Original Research
Pharmacokinetics of a fixed-dose glimepiride/sustained-release metformin combination
Kyu-pyo Kim, Kyoung Soo Lim, Bo-Hyung Kim, Hyun-Suk Shin, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang and Kyung-Sang Yu
Price
42.00 $
Volume 50 p. 142 - 149
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 50 – No. 2/2012 (142-149)
Pharmacokinetics of a fixed-dose glimepiride/sustained-release metformin combination
Kyu-pyo Kim1*, Kyoung Soo Lim*, Bo-Hyung Kim, Hyun-Suk Shin, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang and Kyung-Sang Yu
Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea
*Both authors contributed equally to this work.
1Current affiliation: Department of Internal Medicine, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea
Objective: Pharmacokinetic (PK) profiles of glimepiride and metformin have been established for the combination drug as well as each agent individually. However, the PK profiles of a combination drug containing glimepiride and sustainedrelease (SR) metformin have not been reported. To compare the pharmacokinetic profiles of glimepiride/SR metformin (2 mg/500 mg) with the PK of immediate-release (IR) formulations, an open-label, randomized, 3-period, 3-sequence, 3-treatment, crossover study was conducted in 12 healthy subjects. Methods: After a single administration of glimepiride/SR metformin 2 mg/500 mg (Treatment) or glimepiride/metformin IR 2 mg/500 mg (Reference 1), or administration of 2 doses of glimepiride/metformin IR 1 mg/250 mg 12 h apart (Reference 2), serial blood samples were collected and drug concentrations determined by liquid chromatography/ tandem mass spectrometry. PK parameters (Cmax and AUC24) for glimepiride and metformin were log-transformed and compared using a mixed-effects model analysis of variance (ANOVA). The mean differences and 95% confidence intervals (CIs) were back-transformed to obtain geometric mean ratios along with the CIs for the ratios. Results: Treatment demonstrated similar systemic exposures for glimepiride; the geometric mean ratio (95% CIs) for glimepiride AUC24 was 1.05 (0.97 – 1.13) for Treatment relative to Reference 1 and 1.08 (1.00 – 1.17) for Treatment relative to Reference 2. The SR formulation showed a delay in the time to reach maximum concentration for metformin from 1.0 – 4.0 h to 4.0 – 8.0 h and a decreased AUC24 value; the geometric mean ratio for metformin AUC24 was 0.87 (0.74 – 1.03) for Treatment relative to Reference 1 and 0.75 (0.63 – 0.88) for Treatment relative to Reference 2. Conclusions: This study demonstrates for the first time that fixed-dose glimepiride and SR metformin 2 mg/500 mg shows a PK profile similar to that of glimepiride, but with a delayed time to maximum concentration and slightly decreased bioavailability for metformin compared with the IR fixed-dose combination, in healthy volunteers. PK profiles from this exploratory study will be helpful in designing and conducting further studies in diabetic patients.Correspondence to:
Kyung-Sang Yu, MD, PhD
Department of Pharmacology and Clinical Pharmacology
National University College of Medicine and Hospital
101 Daehangno, Jongno-gu, Seoul 110-744, Korea
Email: [email protected]
Bioavailability Section
Pharmacokinetics and bioequivalence of sildenafil granules and sildenafil tablets in Korean healthy volunteers
Renhua Zheng and Bo-Hyung Kim
Price
42.00 $
Volume 52 p. 530 - 536
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 6/2014 (530-536)
Pharmacokinetics and bioequivalence of sildenafil granules and sildenafil tablets in Korean healthy volunteers
Renhua Zheng1 and Bo-Hyung Kim1,2
1Department of Clinical Pharmacology and Therapeutics, and 2East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea
Background: A sildenafil tablet formulation as a PDE-5 inhibitor is widely used for the treatment of erectile dysfunction. Recently, a fine granular formulation of sildenafil was developed by a domestic Korean pharmaceutical company. Objectives: This study was performed to compare the bioavailability of sildenafil fine granules with that of sildenafil tablets for assessing bioequivalence in 40 healthy male volunteers. Methods: This was an open-label, randomized sequence, single-dose, two-period, and two-treatment crossover study. Half of the volunteers received a single dose of sildenafil fine granule 50 mg and then sildenafil tablet 50 mg after a 7-day washout period. The remaining half of volunteers received the tablet first and the the granule with the same washout period. 10- mL blood samples were serially sampled to measure the concentrations of sildenafil and the N-desmethyl metabolite. Tolerability was assessed during the study. Results: The pharmacokinetic parameters of sildenafil were similar between granular and tablet formulations. The 90% CI of geometric mean ratios (sildenafil granule/tablet) for the pharmacokinetic parameters of sildenafil were within 0.8 – 1.25, as a bioequivalent acceptable range; 1.111 (90% CI, 1.002 – 1.231) for maximum plasma concentration (Cmax) and 1.092 (1.019 – 1.117) for area under the concentration- time curve from time zero to time of last measurable concentration (AUClast). Also, the 90% CI of geometric mean ratios for Cmax and AUClast of the metabolite were within 0.8 – 1.25. Both formulations were well tolerated by volunteers. Conclusion: This study confirmed that sildenafil granules and sildenafil tablet are bioequivalent with regards to pharmacokinetics of sildenafil and N-desmethyl sildenafil.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
East-West Medical Research Institute
Kyung Hee University College of Medicine
and Hospital Seoul, Republic of Korea
23 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-872, Korea
Email: [email protected]
Bioavailability Section
Pharmacokinetic and bioequivalence assessment of two formulations of tianeptine sodium in healthy male volunteers
Renhua Zheng and Bo-Hyung Kim
Price
42.00 $
Volume 52 p. 817 - 823
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 9/2014 (817-823)
Pharmacokinetic and bioequivalence assessment of two formulations of tianeptine sodium in healthy male volunteers
Renhua Zheng1 and Bo-Hyung Kim1,2
1Department of Clinical Pharmacology and Therapeutics, and 2East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea
Background: Tianeptine is widely used for controlling depressive symptoms. Objective: The aim of this study was to evaluate the bioequivalence between the generic (test) formulation containing tianeptine sodium 12.5 mg and the branded (reference) formulation Stablon® with regard to their pharmacokinetic profiles. Methods: A randomized, two-sequence, two-treatment crossover study was conducted in healthy male Korean volunteers. All of the enrolled subjects were allocated to one of two sequence groups. They were administered a tablet of the test or reference formulation and then administered the alternative formulation after a 7-day washout period. The blood samples were taken before dosing and at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 10 hours after dosing. The plasma concentrations of tianeptine were analyzed using high-performance liquid chromatography with tandem mass spectrometer. Tolerability was assessed throughout the study. Results: The pharmacokinetic parameters were assessed in the 40 subjects who completed the study. The tianeptine Cmax for the test formulation was 283.13 ± 57.58 ng/mL (mean ± SD) and that for the reference formulation was 272.50 ± 59.00 ng/mL. The AUClast of tianeptine was 803.24 ± 180.94 ng×h/mL for the test formulation and 792.27 ± 180.93 ng×h/mL for the reference formulation. The geometric mean ratio (%) of the test to reference formulation was 104.04 (90% CI, 99.66 – 108.61) for Cmax and 101.30 (98.01 – 104.71) for AUClast. Clinically significant adverse events were not reported during the study. Conclusion: The test and reference formulations of tianeptine were bioequivalent with regard to the pharmacokinetic parameters of Cmax and AUClast. Both formulations were tolerated by all of the participants.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
East-West Medical Research Institute
Kyung Hee University College of Medicine and Hospital Seoul
23 Kyungheedae-ro, Dongdaemun-gu, Seoul
130-872, Korea
Email: [email protected]
Original
Pharmacokinetic evaluation of a newly developed piperazine dithioctate formulation in healthy volunteers
Renhua Zheng, Hyung Ho Song, Young Ee Kwon, and Bo-Hyung Kim
Price
42.00 $
Volume 52 p. 1083 - 1092
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 12/2014 (1083-1092)
Pharmacokinetic evaluation of a newly developed piperazine dithioctate formulation in healthy volunteers
Renhua Zheng1, Hyung Ho Song3, Young Ee Kwon3, and Bo-Hyung Kim1,2
1Department of Clinical Pharmacology and Therapeutics, 2East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, and 3Korea Pharmaceutical Test & Research Institute (KPTR), Seoul, Republic of Korea
Background: The formulation investigated as reference contains thioctic acid which is known to be poorly soluble in water and have some instability during storage at high temperature. To overcome these limitations, a new piperazine dithioctate (PDT) tablet formulation was developed by a domestic pharmaceutical company in Korea. Objective: The aim of this clinical study was to evaluate the pharmacokinetic characteristics of PDT in healthy volunteers. Methods: This study consisted of two clinical trials. In the part 1 study, a randomized, singledose, parallel study was performed with 24 healthy volunteers. All of the subjects were administered one of the three study formulations, Thioctacid® HR (High Release) as the reference, PDT-1 or PDT-2 (each containing thioctic acid 600 mg), respectively. To determine the harmacokinetic characteristics, blood samples were serially collected at pre-dose and at pre-defined timepoints after dosing. In the part 2 study, a randomized, single-dose, two-way crossover study was conducted with 48 subjects. All of the subjects were administered both the reference and PDT-2 formulations, with a 7-day washout period between the two medications. Blood samples were collected at the same timepoints as in the part 1 study. Tolerability was evaluated throughout the study. Results: 23 volunteers completed the part 1 study. The maximum plasma concentration (Cmax) of thioctic acid after administration of the reference tablet was 4.08 ± 2.35 μg/mL (means ± SD), and the Cmax of PDT-1 and PDT-2 was 3.53 ± 2.87 μg/mL and 4.15 ± 1.62 μg/mL, respectively. The AUClast value was 2.96 ± 1.13 μg×h/mL for the reference, 2.84 ± 1.12 μg×h/mL for PDT-1, and 3.30 ± 1.32 μg×h/mL for PDT-2. 42 volunteers completed the part 2 study. The Cmax of reference and PDT-2 was 5.59 ± 3.07 μg/mL and 5.14 ± 3.18 μg/mL, respectively. The AUClast value was 4.01 ± 1.65 μg×h/mL for the reference and 3.96 ± 1.47 μg×h/mL for PDT-2. The geometric mean ratios (PDT-2/reference) and the 90% CI for Cmax and AUClast were 0.93 (0.78 – 1.11) and 1.01 (0.94 – 1.09), respectively. Conclusion: Both studies suggested that the pharmacokinetic profile of the newly developed piperazine dithioctate formulation was comparable to the pharmacokinetic profile of the reference tablet. Both study tablets were well tolerated in all of the subjects.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
East-West Medical Research Institute
Kyung Hee University College of Medicine and Hospital
23 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-872, Korea
Email: [email protected]
Bioavailability Section
Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers
Sang-Min Baek, Renhua Zheng, Eun-Jung Seo, Dae-Yeon Hwang, and Bo-Hyung Kim
Price
42.00 $
Volume 53 p. 980 - 986
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 11/2015 (980-986)
Pharmacokinetic comparisons of two acetyl-L-carnitine formulations in healthy Korean volunteers
Sang-Min Baek1, Renhua Zheng1, Eun-Jung Seo1, Dae-Yeon Hwang1, and Bo-Hyung Kim1,2
1Department of Clinical Pharmacology and Therapeutics, and 2East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea
Background: Acetyl-L-carnitine (ALC) has demonstrated neuroprotective effects in several experiments and is widely prescribed to reduce cognitive impairment in Alzheimer’s disease patients or manage neuropathic symptoms in diabetic patients. Objectives: This study was designed to assess the pharmacokinetic (PK) bioequivalence between a new generic (test) formulation of ALC hydrochloride 590 mg and a branded (reference) formulation of ALC hydrochloride 590 mg in healthy Korean male volunteers. Methods: This was a randomizedsequence, single-dose, two-way crossover study. All subjects randomly received one formulation of the test or reference tablet and the other formulation with a 7-day washout period. Blood samples (7 mL) were collected immediately before dosing, and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours postdose. The plasma concentrations of ALC were analyzed using liquid chromatography tandem mass spectrometry. Tolerability was assessed throughout the study. Results: The PK profiles of both formulations showed similar rends. The mean (± SD) baseline (predose) concentration of ALC was 1.23 ± 0.31 μg/mL and 1.09 ± 0.30 μg/mL for the test and the reference formulations, respectively. The mean Cmax for the test and reference formulations were 1.74 ± 0.43 μg/mL and 1.68 ± 0.48 μg/mL, respectively. The mean AUClast of ALC was 12.96 ± 1.89 μg×h/mL and 12.49 ± 2.44 μg×h/mL for the test and reference formulations, respectively. The geometric mean ratios of test/reference (90% CI) were 1.050 (0.960 – 1.149) for Cmax and 1.048 (1.000 – 1.099) for AUClast. Both formulations were well tolerated in all treatment groups. Conclusion: The test and the reference formulations of ALC were bioequivalent with regard to the PK parameters.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
East-West Medical Research Institute
Kyung Hee University College of Medicine and Hospital
Seoul, Republic of Korea, 23 Kyungheedae-ro,
Dongdaemun-gu, Seoul 130-872, Korea
Email: [email protected]
Original
Efficient strategy for obtaining reliable pharmacokinetic parameters in population compartmental approaches
Junhee Lee, Dongwoo Kang, Euitae Kim, and Bo-Hyung Kim
Price
42.00 $
Volume 54 p. 11 - 18
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 1/2016 (11-18)
Efficient strategy for obtaining reliable pharmacokinetic parameters in population compartmental approaches
Junhee Lee1, Dongwoo Kang2, Euitae Kim3, and Bo-Hyung Kim4
1Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea, 2Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Pharma Development, Edison, NJ, USA, 3Department of Neuropsychiatry, Seoul National University Bundang Hospital, Gyeonggi-do, and 4Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea
Objective: This study aimed to suggest efficient strategies for obtaining reliable pharmacokinetic (PK) parameters in population compartmental approach (PCA) a early-phase or resource-limited clinical trials with limited data. Methods: This study employed plasma concentration of olanzapine, an antipsychotic drug, from a bioequivalence study. To assess bias and precision of PK parameters that were estimated from limited data, this study utilized simulations with the generation of small-size datasets (SSD) and minimal-sampling datasets (MSD) that consisted of limited volunteers and PK samplings per volunteer, respectively. Results: Clearance (CL) estimates were the most robust, volume of the central (Vc) and peripheral compartment (Vp) were moderately affected, and absorption rate constant (Ka) and intercompartmental clearance (Q) were very sensitive with limited dataset. MSD had more impact on the bias and precision of PK parameter estimation than SSD. Conclusions: Performance of PK parameter estimation evaluated by bias and precision from simulation datasets was better in SSD than MSD. This finding implies that collecting more PK samplings is a more efficient strategy than recruiting more volunteers in order to obtain informative results in performing PCA.Correspondence to:
Euitae Kim, MD, PhD
Department of Neuropsychiatry
Seoul National University Bundang Hospital
82 Gumi-ro173 Beon-gil, Bundang-gu,
Seongnamsi, Gyeonggi-do, 463-707, Republic of Korea
or
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
23, Kyungheedae-ro, Dongdaemun-gu,
Seoul 130-872, Republic of Korea
Email: [email protected] or [email protected]
Original Research
Compartmental approach to assess bioequivalence compared to the noncompartmental approach
Sung Eun Kim, Renhua Zheng, Dongwoo Kang, and Bo-Hyung Kim
Price
42.00 $
Volume 54 p. 442 - 449
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 6/2016 (442-449)
Compartmental approach to assess bioequivalence compared to the noncompartmental approach
Sung Eun Kim1, Renhua Zheng2, Dongwoo Kang3, and Bo-Hyung Kim2
1Department of Pharmacy, Seoul National University Hospital, 2Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Republic of Korea, and 3Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Pharma Development, Edison, NJ, USA
Objective: The objective of this study is to evaluate the relative performance of individual or population compartmental analysis (ICA or PCA) vs. noncompartmental analysis (NCA) in estimating the systemic exposures of drugs to assess bioequivalence (BE) between original and generic formulations in the case of limited datasets. Methods: BE study data of adefovir, finasteride, and tiropramide were chosen. The analyses were performed for the 1) original dataset, 2) limited dataset with small size for which the number of subjects was decreased to half, and 3) limited dataset with minimal-sampling timepoint of 9 samples. As for NCA and ICA, the Cmax and AUCinf were estimated using WinNonlin®. The PCA was implemented in NONMEM® and then Monte Carlo simulation was utilized to generate 10,000 sets of Cmax and AUCinf. Results: The 90% confidence intervals (CIs) of the original datasets of the 3 drugs were all within BE acceptance criteria regardless of the analysis method. For small-samplesize datasets of adefovir and finasteride, BE results were maintained. In tiropramide, the lower boundary of CI computed from ICA or PCA results was less than 0.800 for the 3 small sample sizes (n = 22, 16, 10), but that of NCA results was less than 0.800 for only the smallest sample size (n = 10). As for the minimal-sampling timepoint, results were within the BE acceptance criteria for all of the 3 analyses. Conclusions: Compartmental approaches can provide a complementary method for BE assessment, as well as being used for restricted-design studies.Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
23 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-872, Korea
Email: [email protected]
Bioavailability Section
A bioequivalence study of two omeprazole formulations in healthy male volunteers
Yu Kyong Kim, Seonghae Yoon, Kyung-Sang Yu, Bo-Hyung Kim, and Sung-Vin Yim
Price
42.00 $
Volume 54 p. 928 - 934
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 11/2016 (928-934)
A bioequivalence study of two omeprazole formulations in healthy male volunteers
Yu Kyong Kim1, Seonghae Yoon1, Kyung-Sang Yu1, Bo-Hyung Kim2, and Sung-Vin Yim2
1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, and 2Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
Objective: This study had a single-dose, randomized, open-label, 2-period, and 2-sequence crossover design to evaluate pharmacokinetic (PK) bioequivalence between the test and reference formulations. Methods and materials: Of the 34 healthy male volunteers enrolled, 4 were excluded owing to consent withdrawal before drug administration and the remaining 30 subjects were administered 20 mg each of the test and reference formulations of omeprazole. The blood samples for PK analysis were collected at the scheduled time-points, prior to dosing to 10 hours after dosing. Plasma concentrations of omeprazole were quantified by a liquid chromatography-tandem mass spectrometry method. Bioequivalence was assessed according to current guidelines issued by regulatory authorities. Results: The plasma concentration-time profiles of omeprazole were similar between the reference and test drugs. The geometric mean ratios (90% confidence interval: CI) of test to reference were 0.9104 (0.8538 – 0.9708) for peak plasma concentration (Cmax) and 0.9304 (0.8836 – 0.9796) for area under the plasma concentration-time curve from time zero to time of last measureable concentration (AUC0–t). Conclusion: The results from the PK analysis suggested that the reference and test formulations of 20 mg omeprazole capsules were bioequivalent in healthy male subjects.Correspondence to:
Sung-Vin Yim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea
Email: [email protected]
Bioavailability Section
Comparative pharmacokinetic and bioequivalence evaluation of two formulations of morniflumate 350-mg tablets in healthy male subjects
Heechan Lee, Sung-Vin Yim, Bo-Hyung Kim, SeungHwan Lee
Price
42.00 $
Volume 55 (2017) p. 95 - 101
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 1/2017 (95-101)
Comparative pharmacokinetic and bioequivalence evaluation of two formulations of morniflumate 350-mg tablets in healthy male subjects
Heechan Lee1,2, Sung-Vin Yim3, Bo-Hyung Kim3,4, SeungHwan Lee2
1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, College of Medicine and Hospital, 3Department of Clinical Pharmacology and Therapeutics, and 4East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
Background: Morniflumate is a nonsteroid anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-1, 2 (COX-1, 2). Objective: This study aimed to compare the pharmacokinetics (PKs) and assess the bioequivalence of two different formulations of morniflumate 350-mg tablets in healthy Korean male subjects. Methods: A randomized, single-dose, two-period, two-sequence crossover study was conducted with 38 subjects. Subjects received a single dose of two tablets of either a test or a reference formulation and the alternated formulation in the next period. Serial blood samples for the PK analysis were collected over 12 hours. PK parameters were determined by a noncompartment analysis. PK parameters, including the maximum concentration (Cmax) and the area under-the-concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) were compared in bioequivalence tests. Results: The Cmax of the test and reference formulations were 985.72 ± 6.80 mg/L and 947.09 ± 6.73 mg/L, respectively, while the AUClast values were 2675.92 ± 7.84 mg×h/L and 2653.06 ± 7.78 mg×h/L, respectively. The geometric mean ratios (90% confidence interval) of the test formulation to the reference formulation for Cmax and AUClast were 1.0715 (0.9469 – 1.2124) and 1.0592 (0.9592 – 1.1695), respectively. Conclusions: The new formulation of morniflumate 350-mg tablet showed a PK profile similar to that of the marketed formulation, and the results of this study fell within in the conventional criteria of bioequivalence.
Correspondence to:
SeungHwan Lee, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Seoul National University Hospital and College of Medicine
Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
Email: [email protected]
Bioavailability Section
Pharmacokinetic comparison of two formulations of talniflumate 370 mg tablets in healthy Korean volunteers
Yun Kim, Sung- Yim, Bo-Hyung Kim, SeungHwan Lee
Price
42.00 $
Volume 55 (2017) p. 102 - 108
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 1/2017 (102-108)
Pharmacokinetic comparison of two formulations of talniflumate 370 mg tablets in healthy Korean volunteers
Yun Kim1#2, Sung- Yim3, Bo-Hyung Kim3#4, SeungHwan Lee2
1Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University, College of Medicine and Hospital, 3Department of Clinical Pharmacology and Therapeutics, and 4East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
Background: Talniflumate, a prodrug of niflumic acid, is a potent analgesic and anti-inflammatory drug that has been widely used for the treatment of rheumatoid diseases. Objective: The aim of this study was to compare the pharmacokinetics and to evaluate the bioequivalence of two formulations of talniflumate 370 mg tablets (test formulation: Flumagen® 370 mg tablet; reference formulation: Somalgen® 370 mg tablet). Methods: A randomized, open-label, single dose, two-sequence, two-period crossover clinical study was conducted. After oral administration of the study drug in each period, blood samples were collected up to 15 hours post-dose. The plasma concentration of niflumic acid, a metabolite of talniflumate, was determined using HPLC-MS/MS. The pharmacokinetic parameters were estimated by non-compartmental method. Results: The maximum plasma concentration (Cmax) and area under the concentration-time curve from zero to the time point with the last measurable concentration (AUClast) for the test formulation were 290.7 ± 199 µg/L and 1,154 ± 643 µg×h/L, respectively, and the corresponding values for the reference formulation were 286.8 ± 193 µg/L and 1,151 ± 577 µg×h/L, respectively. The geometric mean ratio and 90% confidence intervals (CI) of the test formulation to the reference formulation for the Cmax and AUClast were 0.983 (0.829 – 1.166) and 0.979 (0.856 – 1.121), respectively. Conclusions: The pharmacokinetic profiles of the test and reference formulations were found not to be significantly different, meeting the Korean regulatory criteria for bioequivalence.
Correspondence to:
SeungHwan Lee, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Seoul National University
College of Medicine and Hospital
Daehak-ro, Jongno-gu, Seoul, 03080, Korea
Email: [email protected]
Bioavailability Section
Bioequivalence of two formulations of pregabalin 150-mg capsules under fasting conditions in healthy male subjects
Hyun Lee, SeungHwan Lee, Sung-Vin Yim, Bo-Hyung Kim
Price
42.00 $
Volume 55 (2017) p. 171 - 176
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 2/2017 (171-176)
Bioequivalence of two formulations of pregabalin 150-mg capsules under fasting conditions in healthy male subjects
Hyun Lee1,2, SeungHwan Lee2, Sung-Vin Yim3, Bo-Hyung Kim3,4
1Program in Biomedical Radiation Sciences, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 3Department of Clinical Pharmacology and Therapeutics, and 4East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
Background: Pregabalin binds to the α2δ auxiliary subunit of voltage-gated calcium channels, which are widely distributed throughout the central and peripheral nervous systems and modulate calcium-dependent neurotransmitter release. Pregabalin is indicated for the treatment of peripheral and central neuropathic pain, partial seizures with or without secondary generalization, and treatment of generalized anxiety disorder (GAD). Objective: The purpose of this study was to assess the bioequivalence of two different formulations of pregabalin 150-mg capsules in healthy Korean male subjects under fasting conditions. Methods: This bioequivalence study was based on an open-label, single-dose, randomized, 2-period, 2-sequence crossover design with a washout period of 7 days. Blood samples for pharmacokinetic (PK) evaluation were collected up to 24 hours postdose. Plasma concentrations of pregabalin were determined using a validated LC-MS/MS method. PK parameters were determined using noncompartmental analysis. Bioequivalence was assumed if the 90% confidence intervals (CIs) for the test/reference ratios of log-transformed Cmax and AUClast values met the bioequivalence criteria specified by Korean regulatory guidelines (90% CI 0.8 – 1.25). Results: The extent of exposure in terms of AUClast amounted to 26,018.3 – 3,580.8 µg×h/L for the test formulation and 25,680.2 ± 3,083.6 µg×h/L for the reference formulation. Cmax reached values of 4,782.7 ± 1,124.2 µg/L and 4,654.0 ± 911.4 µg/L for the test product and reference product, respectively. The geometric mean ratio and 90% CIs of the test product to the reference product were 1.0132 (0.9862 – 1.0351) for AUClast and 1.0153 (0.9351 – 1.1044) for Cmax, which were well within the range necessary to establish bioequivalence (90% CI 0.8 – 1.25). Conclusions: The bioequivalence between test and reference formulations under fasting conditions was confirmed both in terms of the rate and extent of absorption.
Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
23 Kyungheedae-ro, Dongdaemun-gu,
Seoul 130-872, Korea
Email:
[email protected]
Bioavailability Section
Bioequivalence assessment of tulobuterol transdermal delivery system in healthy subjects
Sang-In Park and Bo-Hyung Kim
Price
42.00 $
Volume 56 (2018) p. 381 - 386
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 56 – No. 8/2018 (381-386)
Bioequivalence assessment of tulobuterol transdermal delivery system in healthy subjects
Sang-In Park1#2, Bo-Hyung Kim1#2#3#4
1Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, 2East-West Medical Research Institute, Kyung Hee University, Seoul, 3Department of Clinical Pharmacology and Therapeutics, College of Medicine, and 4Department of Biomedical Science and Technology, Kyung Hee University, Seoul, Republic of Korea
Objective: The purpose of this study was to evaluate the bioequivalence in the pharmacokinetics of two 2-mg tulobuterol transdermal delivery systems (TDSs) in healthy subjects. Materials and methods: The pharmacokinetic (PK) analysis was performed using data from a randomized, open-label, single-dose, two-way, two-period, crossover study. Eligible subjects received either the Bretol® patch (test drug) or Hokunalin® patch (reference drug) in sequence according to their allocated group. Serial blood samples for PK analyses were collected for up to 48 hours after tulobuterol TDS application. The PK parameters, including the maximum concentration (C<sub>max</sub>) and area under the curve from time zero to the last quantifiable concentration time (AUC<sub>last</sub>), were estimated by using noncompartmental analysis. The geometric mean ratios (GMRs) of the C<sub>max</sub> and AUC<sub>last</sub> and their 90% confidence intervals (CIs) were estimated. Results: A total of 27 subjects completed the study as planned. The concentration-time profiles of tulobuterol were similar in both formulations. The GMRs (90% CIs) of C<sub>max</sub> and AUC<sub>last</sub> were 0.9443 (0.8790 – 1.0144) and 0.9600 (0.8660 – 1.0642), respectively. Conclusion: The PK profiles of both tulobuterol TDSs were comparable. In addition, the 90% CIs of the GMR were within the bioequivalence criteria of 0.800 – 1.250. Therefore, the Bretol® patch can be used as an alternative to the Hokunalin® patch for the treatment of patients with asthma and chronic obstructive pulmonary disease.
Correspondence to:
Bo-Hyung Kim, MD, PhD
Department of Clinical Pharmacology and Therapeutics
Kyung Hee University College of Medicine and Hospital
Seoul 02447,
Republic of Korea
Email: [email protected]
Original
Occurrence of metabolic diseases associated with antipsychotic use among Korean patients with schizophrenia
Sunghee Kuk, Seoyoung Kim, Euitae Kim, Bo-Hyung Kim, Woojoo Lee, and Sang-In Park
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Volume 59 (2021) p. 298 - 307
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 4/2021 (298-307)
Occurrence of metabolic diseases associated with antipsychotic use among Korean patients with schizophrenia
Sunghee Kuk1, Seoyoung Kim2, Euitae Kim2, Bo-Hyung Kim3#4#5#6, Woojoo Lee7, and Sang-In Park8
1Department of Statistics, Inha University, Incheon, 2Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, 3Department of Clinical Pharmacology and Therapeutics, Seoul, 4East-West Medical Research Institute, 5Department of Clinical Pharmacology and Therapeutics, College of Medicine, 6Department of Biomedical Science and Technology, Kyung Hee University, 7Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, and 8Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Republic of Korea
Objective: Metabolic side effects of antipsychotics significantly affect adherence to medication. We aimed to identify factors associated with the occurrence of metabolic diseases among Korean patients with schizophrenia (SCZ) from the national health insurance system database. We evaluated the frequency of antidiabetic and antihyperlipidemic use after diagnosis of SCZ according to typical or atypical antipsychotic use.
Materials and methods: Among the 43,800 patients diagnosed with SCZ between 2008 and 2012, 29,591 patients who had no metabolic diseases before the diagnosis were included in the analysis to investigate the occurrence of metabolic diseases associated with antipsychotic use. The associations between the development of metabolic diseases and patient characteristics were evaluated using logistic regression analysis.
Results: Use of both typical and atypical antipsychotics (multivariate-adjusted odds ratio (OR), 1.2513; 95% confidence interval (CI), 1.0953 – 1.4294) was associated with higher incidence of metabolic diseases than without their use. Among the atypical antipsychotics, use of clozapine (multivariate-adjusted OR, 1.1959; 95% CI, 1.0086 – 1.4179) and quetiapine (multivariate-adjusted OR, 1.1284; 95% CI, 1.0446 – 1.2189) showed higher incidence of metabolic diseases compared to that without their use. Among the patients using ≥ 1 type of antidiabetic or antihyperlipidemic agents within 6 years after diagnosis of SCZ, the proportion of patients using only atypical antipsychotics was greater than those using only typical antipsychotics.
Conclusion: The use of both typical and atypical antipsychotics, and clozapine and quetiapine treatment, may be associated with the occurrence of metabolic diseases in patients with SCZ. Additional prospective studies with accurate dosage information are needed to validate our findings.Correspondence to:
Sang-In Park, MD, PhD
1 Gangwondaehakgil, Chuncheon-si,
Gangwon-do 24341, Republic of Korea
Email: [email protected]
