Bioavailability Section
Relative bioavailability of levodropropizine 60 mg capsule and syrup formulations in healthy male Korean volunteers: a singledose, randomized-sequence, open-label, two-way crossover study
Jae-Won Jang, Ji-Hyung Seo, Min-Ho Jo, Young-Joo Lee, Young-Wuk Cho, Sung-Vin Yim and Kyung-Tae Lee
Price
42.00 $
Volume 51 p. 152 - 160
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 2/2013 (152-160)
Relative bioavailability of levodropropizine 60 mg capsule and syrup formulations in healthy male Korean volunteers: a singledose, randomized-sequence, open-label, two-way crossover study
Jae-Won Jang1, Ji-Hyung Seo1,3, Min-Ho Jo1,2, Young-Joo Lee2, Young-Wuk Cho3, Sung-Vin Yim4 and Kyung-Tae Lee1,2,3,5
1Department of Pharmaceutical Biochemistry, 2Department of Life and Nanopharmaceutical Science, College of Pharmacy, 3Department of Biomedical Science, 4Department of Clinical Pharmacology, College of Medical Science, Kyung Hee University, and 5Kyung Hee Drug Analysis Center, Seoul, Republic of Korea
Background: Levodropropizine is an oral non-opioid anti-tussive drug used in treatment of cough. A new generic 60 mg capsule formulation of levodropropizine has recently been developed. Objectives: The aim of this study was to assess the pharmacokinetics and bioequivalence of the test (capsule) formulation and reference (syrup) formulation of levodropropizine (60 mg) in healthy, fasted, male Korean volunteers. Methods: This was a single-dose, randomized sequence, open-label, 2-period crossover study conducted in healthy male Korean volunteers in the fasted state at Kyung Hee University Medical Center (Seoul, Republic of Korea). A single oral dose of the test or reference formulation was followed by a 1-week washout period, after which subjects received the alternative formulation. Blood samples were collected at 0 (predose), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after study drug administration. Plasma concentration of levodropropizine was determined using a validated liquid chromatography tandem mass spectrometry (LCMS/ MS) method. The formulations were considered bioequivalent if the 90% CIs for Cmax, AUC0–12h and AUC0–∞ were within the predetermined bioequivalence range (80 – 125%, according to the guidelines of the Korea Food and Drug Administration (Korea FDA)). Tolerability was evaluated throughout the study based on vital sign measurements, laboratory analysis (blood biochemistry, hematology, hepatic function and urinalysis) and subject interviews concerning adverse events (AEs). Results: A total of 36 male Korean subjects (mean (SD) age, 23.9 (2.4) years (range 19 – 30 years); height, 176.2 (6.1) cm (range 161 – 190 cm); weight, 69.8 (9.1) kg (range 54.0 – 92.2 kg); body mass index, 22.4 (2.1) kg/m2 (range 19.1 – 28.3 kg/m2)) was enrolled and completed the study. The mean values for Cmax, tmax, AUC0–12h, and AUC>sub>0–∞ with the test formulation of levodropropizine were 331.51 ng/ml, 0.60 hours, 784.32 ng×h/ml, and 825.82 ng×h/ml, respectively; for the reference formulation, the values were 332.81 ng/ml, 0.44 hours, 726.46 ng×h/ml, and 769.46 ng×h/ ml, respectively. The 90% CIs for the logtransformed ratios of Cmax (92.74 – 111.24), AUC0–12h (104.31 – 113.67) and AUC0–∞ (103.87 – 113.57) were within the predetermined range for the assumption of bioequivalence. No serious adverse events were reported. Conclusions: This single-dose (60 mg) study found that the test (capsule) and reference (syrup) formulations of levodropropizine met the regulatory criterion for assuming bioequivalence in these healthy, fasted, male Korean subjects. Both formulations were well tolerated in the population studied. Korea FDA registration number: BED-1784.Correspondence to:
Kyung-Tae Lee, PhD
Department of Pharmaceutical Biochemistry
College of Pharmacy, Kyung Hee University
1 Hoegi-Dong Dongdaemun-gu
130-701, Seoul, Republic of 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
The pharmacokinetic comparison and bioequivalence evaluation of two 10-mg baclofen formulations in healthy male subjects
Sumin Yoon, SeungHwan Lee, Kyung-Sang Yu, Sung-Vin Yim, Bo-Hyung Kim
Price
42.00 $
Volume 55 (2017) p. 194 - 200
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 2/2017 (194-200)
The pharmacokinetic comparison and bioequivalence evaluation of two 10-mg baclofen formulations in healthy male subjects
Sumin Yoon1, SeungHwan Lee1, Kyung-Sang Yu1, Sung-Vin Yim2, Bo-Hyung Kim2#3
1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Department of Clinical Pharmacology and Therapeutics, and 3East-West Medical Research Institute, Kyung Hee University College of Medicine and Hospital, Seoul, Korea
Backgrounds: Baclofen is used as a skeletal muscle relaxant for multiple sclerosis patients. It depresses the transmission of monosynaptic and polysynaptic reflex by stimulating GABAβ (gamma-aminobutyric acid) receptors. Objectives: The aim of this study was to compare the pharmacokinetic characteristics of two 10-mg baclofen formulations and to assess bioequivalence. Methods: A randomized, single-dose, two-period, two-sequence crossover study was conducted in healthy male subjects. Each subject received the test or reference formulations. After washout period, all subjects received the alternative formulation. Blood samples were collected for up to 24 hours after the dose in each period. Pharmacokinetic (PK) parameters, including tmax, Cmax, and AUClast were calculated by noncompartmental methods. The geometric mean ratio (GMR) of the test to the reference formulation and its 90% confidence interval (CI) for Cmax and AUClast were calculated for assessment of bioequivalence. Results: A total of 22 subjects completed the study. The median tmax of the test and the reference formulation were 1.50 and 1.25 hours, respectively. The mean (± SD) Cmax of the test and the reference formulation were 141.401 ± 29.447 ng/mL and 138.837 ± 31.392 ng/mL, respectively. The mean (± SD) AUClast of the two formulations were 702.404 ± 82.149 ng×h/mL and 726.803 ± 90.638 ng×h/mL, respectively. The GMR (90% CI) of the test to the reference formulation for the Cmax and AUClast were 1.0306 (0.9564 – 1.1106) and 0.9674 (0.9437 – 0.9916), respectively. Conclusions: The two different baclofen 10-mg formulations had similar PK profiles and were bioequivalent based on Cmax and AUClast.
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 02447, 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]
