Volume 52, No. 11/2014(November)
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Original
Treatment persistence evaluation of tamoxifen and aromatase inhibitors in breast cancer patients in early and late stage disease
Nina Schmidt, Karel Kostev, Achim Jockwig, Iannis Kyvernitakis, Ute-Susann Albert, and Peyman Hadji
Price
42.00 $
Page No. 933
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (933-939)
Treatment persistence evaluation of tamoxifen and aromatase inhibitors in breast cancer patients in early and late stage disease
Nina Schmidt1, Karel Kostev1,3, Achim Jockwig2, Iannis Kyvernitakis3, Ute-Susann Albert3, and Peyman Hadji3
1IMS Health, Frankfurt am Main, 2Fresenius University of Applied Sciences, Health and Social Faculty, Idstein, and 3Philipps-University of Marburg, Department of Gynecology, Gynecological Endocrinology and Oncology, Marburg, Germany
Background: The aim of our study was to analyze the persistence with tamoxifen (TAM) and aromatase inhibitors (AIs) in postmenopausal women with hormone-receptor-positive breast cancer (BC) in early and late stage disease. Methods: This study based on data from The IMS Oncology Analyzer (OA) including retrospective longitudinal patient treatment histories from diagnosis for all cancer types. 4,626 patients with a diagnosis of breast cancer with current or terminated treatment with TAM or AIs between January 2003 and March 2012 in Germany were included. Results: Our results indicate a significantly increased risk for treatment discontinuation for patients in the age groups of 41 – 50 and 51 – 60 years compared to older patients as well as in patients with a stage IV tumor compared to patients with lower stage tumors. If treatment was initiated by a gynecologist, patients are less likely to discontinue their therapy compared to treatment initiated by an oncologist. Furthermore, the risk of therapy break up was significantly lower in patients treated in an office-based setting compared to the reference group of patients treated in general hospitals. Conclusion: In conclusion, persistence with endocrine treatment in woman with hormone-receptor-positive breast cancer is low, especially in later stage disease, and needs to be significantly increased to improve outcome in clinical practice. Further research is required to understand this complex, but important aspect.Correspondence to:
Dr. Karel Kostev
Senior Research Advisor
CES LifeLink – Epidemiology and Pharmacovigilance
IMS HEALTH GmbH & Co. OHG
Darmstädter Landstraße 108
60598 Frankfurt am Main, Germany
Email: [email protected]
Original
Fluoroquinolones in pediatrics: review of hospital prescription use over 2 years
Mathieu Genuini, Sonia Prot-Labarthe, Olivier Bourdon, Catherine Doit, Yannick Aujard, Jérôme Naudin, and Mathie Lorrot
Price
42.00 $
Page No. 940
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (940-947)
Fluoroquinolones in pediatrics: review of hospital prescription use over 2 years
Mathieu Genuini1, Sonia Prot-Labarthe2, Olivier Bourdon2,3, Catherine Doit4, Yannick Aujard5, Jérôme Naudin6, and Mathie Lorrot1,7
1Department of General Pediatrics, 2Pharmacy Department, Hôpital Robert-Debré, AP-HP, 3Laboratoire Educations et Practiques des Santé, Université Paris XIII, Bobigny, 4Microbiology Department, 5Neonatal Intensive Care Unit, 6Intensive Care Unit, Hôpital Robert-Debré, AP-HP, and 7UMRS 1123 ECEVE, University Paris Diderot, Sorbonne Paris Cité, France
Objective: Numerous studies have shown that the tolerance of children to fluoroquinolones (FQs) is satisfactory, and some indications have been recently agreed upon. However, vigilance is required when prescribing FQ to children. The aim of our study was to describe the prescription of FQs to children hospitalized in our hospital. Materials and methods: This is a chart retrospective observational study at the Robert-Debré teaching Hospital between January 2009 and December 2010. Data was collected about patients (name, sex, weight, age) and prescribed treatments (indication, international nonproprietary names, dose, number of doses per day, administration route). Quality of collected data was assessed by analyzing the clinical files of 32 randomly selected patients. Results: We analyzed data for 397 patients (3 days – 18 years old and 640 g – 115 kg). Ciprofloxacin was prescribed for 382 patients (96%), ofloxacin for 10 patients (3%), and levofloxacin for 5 patients (1%). Febrile neutropenia was the most common indication (108 patients, i.e., 27%), followed by inflammatory bowel disease (50 patients, 13%). Doses conformed to recommendations for 88% of the patients. Analysis of the 32 cases indicated an overall compliance percentage of 94.4%. Conclusion: This is the first study to collect so much data on FQ prescriptions for hospitalized children. Use in practice went beyond the licensed indication. Doses were consistent with those for recommended indications.Correspondence to:
Dr. Mathieu Genuini
Service de Pédiatrie Générale
Hôpital Robert-Debré
48 boulevard Sérurier
75395, Paris Cedex 19, France
Email: [email protected]
Original
Association between non-adherence to statin and hospitalization for cardiovascular disease and all-cause mortality in a national cohort
Sukyoun Shin, Sunmee Jang, Tae-Jin Lee, and Ho Kim
Price
42.00 $
Page No. 948
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (948-956)
Association between non-adherence to statin and hospitalization for cardiovascular disease and all-cause mortality in a national cohort
Sukyoun Shin1, Sunmee Jang2, Tae-Jin Lee3, and Ho Kim3
1Review and Assessment Research Institute, Health Insurance Review and Assessment Services, Seoul, 2College of Pharmacy, Gachon University, Incheon, and 3Graduate School of Public Health & Institute of Health and Environment, Seoul National University, Seoul, South Korea
Objectives: This study evaluates the effect of adherence to stain on hospitalization for cardiovascular disease and all-cause mortality in South Korea. Methods: We performed a national cohort study on 423,786 individuals using the Korean National Health Insurance Claims Database. The cohort was composed of individuals who were aged between 18 and 84 years, were newly treated with statin, and were followed from 2005 to 2009. Adherence to statin was calculated using medication possession ratio (MPR) and associations between adherence to statin and health outcomes were evaluated using Cox’s proportional hazards regression analysis. Results: Of the study subjects, 41.9% were male, 7.4% were beneficiaries of a tax-financed medical aid program (MAP), 1.5% had prior cardiovascular disease (CVD), 13.0% had diabetes, and 27.5% had hypertension. Non-adherence to statin was found to be associated with an increased risk of cardiovascular hospitalization (HR 2.18, 95% CI: 2.02 – 2.35) and all-cause mortality (HR = 1.75, CI: 1.66 – 1.84). As the age of the study group increased, non-adherence was more strongly associated with the risk of hospitalization for CVD. In addition, the risk of hospitalization for CVD was relatively high in patients who were male, older or MAP beneficiaries, and who had hypertension, diabetes, and high Charlson’s comorbidity index. Conclusions: This study supports that non-adherence to statin is associated with an elevated risk of hospitalization for cardiovascular disease and all-cause mortality.Correspondence to:
Ho Kim, PhD
Graduate School of Public Health &
Institute of Health and Environment
Seoul National University
Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea
Email: [email protected]
Original
Lack of a clinically significant interaction of grapefruit juice with ambrisentan and bosentan in healthy adults
Christoph Markert, Theresia Wirsching, Regina Hellwig, Jürgen Burhenne, Johanna Weiss, Klaus-Dieter Riedel, Gerd Mikus, and Walter E. Haefeli
Price
42.00 $
Page No. 957
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (957-964)
Lack of a clinically significant interaction of grapefruit juice with ambrisentan and bosentan in healthy adults
Christoph Markert, Theresia Wirsching, Regina Hellwig, Jürgen Burhenne, Johanna Weiss, Klaus-Dieter Riedel, Gerd Mikus, and Walter E. Haefeli
Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany
Objective: We assessed the effect of 1 × 300 mL/d and 3 × 300 mL/d grapefruit juice (GFJ) on ambrisentan and bosentan pharmacokinetics in healthy volunteers. Methods: In the ambrisentan study, 12 healthy extensive metabolizers (EM) of CYP2C19 received therapeutic doses of ambrisentan (5 mg q.d. on study days 1 – 11) and GFJ (1 × 300 mL/d on study days 6 – 8 and 3 × 300 mL/d on study days 9 – 11). Ambrisentan pharmacokinetics was assessed on study days 5, 8, and 11. In the bosentan study, 16 healthy EM of CYP2C9, who were stratified into two groups (CYP3A5 expressors (n = 8) and CYP3A5 non-expressors (n = 8)), received bosentan (125 mg b.i.d. on study days 1 – 13) and GFJ (1 × 300 mL/d on study days 8 – 10 and 3 × 300 mL/d on study days 11 – 13). Bosentan pharmacokinetics was assessed on study days 7, 10, and 13. Results: Whereas 1 × 300 mL/d GFJ had no effect on the pharmacokinetics of ambrisentan and its metabolite, 3 × 300 mL/d GFJ increased the exposure with ambrisentan by 8% and the molar plasma metabolic ratio by 22% (both p < 0.05). Correspondingly, the apparent oral clearance of ambrisentan decreased to 92% (p < 0.05). GFJ slightly prolonged tmax of bosentan and increased the metabolic ratio of bosentan/hydroxy-bosentan by 19% (p < 0.05). Conclusion: GFJ had no clinically relevant effect on the pharmacokinetics or safety profile of ambrisentan and bosentan. Therefore, no dose adjustments are needed, and GFJ can be safely co-administered even at very high doses.Correspondence to:
Walter E. Haefeli, MD
Department of Clinical Pharmacology and Pharmacoepidemiology
University Hospital of Heidelberg
Im Neuenheimer Feld 410
69120 Heidelberg, Germany
Email: [email protected]
Original
Single-dose pharmacokinetic properties of esomeprazole in children aged 1 – 11 years with endoscopically proven GERD: a randomized, open-label study
Nader N. Youssef, Eduardo Tron, Vasundhara Tolia, Jennifer E. Hamer-Maansson, Per Lundborg, and Marta Illueca
Price
42.00 $
Page No. 965
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (965-972)
Single-dose pharmacokinetic properties of esomeprazole in children aged 1 – 11 years with endoscopically proven GERD: a randomized, open-label study
Nader N. Youssef1,a, Eduardo Tron2,b, Vasundhara Tolia3,c, Jennifer E. Hamer-Maansson4, Per Lundborg5, and Marta Illueca4
1NPS Pharmaceuticals, Bedminster, NJ, 2Geisinger Health System, Danville, PA, 3Providence Hospital, Southfield, MI, 4AstraZeneca LP, Wilmington, DE, USA, and 5AstraZeneca R&D, Mölndal, Sweden
Affiliations at the time the study was conducted: aGoryeb Children’s Hospital at Atlantic Health, Morristown, NJ, bWomen and Children’s Hospital, Buffalo, NY, and cMichigan State University, Southfield, MI, USA
Objective: To assess the overall exposure after a single dose of esomeprazole in children with gastroesophageal reflux disease (GERD). Materials: Oral esomeprazole administered as an intact capsule with 30 – 180 mL of water, or as an opened capsule mixed with as much as 1 tablespoon of applesauce followed by 30 – 180 mL of water. Methods: In this randomized, open-label study of children aged 1 – 11 years with endoscopically proven GERD, patients weighing 8 – < 20 kg were randomized to a single 5- or 10-mg oral dose of esomeprazole, and patients weighing ≥ 20 kg were randomized to a single 10- or 20-mg oral dose of esomeprazole. Esomeprazole exposure (AUC0–∞), AUC from zero to last measurable concentration (AUC0–t), maximum plasma concentration (Cmax), time to Cmax (tmax), terminal-phase half-life, apparent oral clearance, and apparent volume of distribution were determined. Results: 28 patients were randomized to receive esomeprazole: 14 patients weighing 8 to < 20 kg received esomeprazole 5 mg (n = 7) or 10 mg (n = 7), and 14 patients weighing ≥ 20 kg received esomeprazole 10 mg (n = 6) or 20 mg (n = 8). Children weighing 8 – < 20 kg had a 1.8-fold higher exposure with the 10-mg vs. 5-mg dose (AUC0–∞, 1.32 vs. 0.73 μmol·h/L, respectively); children weighing ≥ 20 kg had a 4.4-fold higher exposure with the 20-mg vs. 10-mg dose (AUC0–∞, 3.06 vs. 0.69 μmol·h/L). Cmax was 2.2-fold higher for the 10-mg vs. 5-mg dose (8 to < 20 kg) and 2.4-fold higher for the 20-mg vs.10-mg dose (≥ 20 kg). Conclusions: The pharmacokinetics of single-dose esomeprazole were dose-dependent in children weighing ≥ 20 kg but not in children weighing 8 to < 20 kg.Correspondence to:
Marta Illueca, MD
1800 Concord Pike B2B-705, PO Box 15437
Wilmington, DE 19850 USA
Email: [email protected]
Original
Pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, and simvastatin following co-administration in healthy volunteers
Sreeraj Macha, Benjamin Lang, Sabine Pinnetti, and Uli C. Broedl
Price
42.00 $
Page No. 973
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (973-980)
Pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, and simvastatin following co-administration in healthy volunteers
Sreeraj Macha1, Benjamin Lang2, Sabine Pinnetti2, and Uli C. Broedl3
1Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, and 3Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
Objective: This study was undertaken to investigate potential drugdrug interactions between the sodium glucose cotransporter 2 inhibitor empagliflozin and simvastatin. Materials and methods: In this open-label, randomized crossover trial, healthy volunteers (median (range) age 36.5 (20 – 50) years) received 3 single-dose treatments: 25 mg empagliflozin (n = 18), 40 mg simvastatin (n = 17), and 25 mg empagliflozin with 40 mg simvastatin (n = 18). Results: Based on standard criteria, simvastatin had no effect on empagliflozin area under the plasma concentration-time curve (AUC0–∞, adjusted geometric mean ratio (GMR): 102.05; 90% CI: 98.90 – 105.29) or maximum plasma concentration (Cmax, GMR: 109.49; 90% CI: 96.91 – 123.69). There were only minor deviations in simvastatin AUC0–∞ (GMR: 101.26; 90% CI: 80.06 – 128.07) and Cmax (GMR: 97.18; 90% CI: 76.30 – 123.77) when co-administered with empagliflozin. Empagliflozin had no effect on AUC0–∞ (GMR: 104.87; 90% CI: 90.09 – 122.07) or Cmax (GMR: 97.27; 90% CI: 84.90 – 111.44) of simvastatin acid, the active metabolite of simvastatin. Adverse events (AEs) were reported for 6 subjects on empagliflozin, 4 on simvastatin, and 5 on co-administered treatment. No serious AEs or investigator-defined drug-related AEs were reported. Conclusion: No relevant drug-drug interaction was observed, and pharmacokinetic results suggest that no dose adjustments for either drug are necessary when empagliflozin and simvastatin are co-administered. Empagliflozin was well tolerated when administered alone or in combination with simvastatin.Correspondence to:
Dr. Sreeraj Macha
Clinical Pharmacokinetics and Pharmacodynamics
Boehringer Ingelheim Pharmaceuticals, Inc.
900 Ridgebury Road, Ridgefield, CT 06877, USA
Email: [email protected]
Original
Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1α, did not increase the systemic exposure of pitavastatin
Hye-In Lee, Chang-Ik Choi, Joon-Ho Sa, Yun-Jeong Lee, Jung-Woo Bae, Choon-Gon Jang, and Seok-Yong Lee
Price
42.00 $
Page No. 981
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (981-985)
Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1α, did not increase the systemic exposure of pitavastatin
Hye-In Lee1, Chang-Ik Choi2, Joon-Ho Sa1, Yun-Jeong Lee1,3, Jung-Woo Bae4, Choon-Gon Jang1, and Seok-Yong Lee1
1School of Pharmacy, Sungkyunkwan University, Suwon, 2College of Pharmacy, Dongguk University-Seoul, Goyang, 3College of Pharmacy, Dankook University, Cheonan, and 4College of Pharmacy, Keimyung University, Daegu, Republic of Korea
Objective: Pitavastatin, a highly potent inhibitor of 3-hydroxy--methylglutarylcoenzyme A reductase, is a known substrate of OATP1B1. Ursodeoxycholic acid (UDCA) inhibits OATP1B1 expression by repressing hepatocyte nuclear factor 1α (HNF1α). Thus, the effects of UDCA on the pharmacokinetics of pitavastatin were investigated in healthy subjects. Methods: An open-label, 2-phase, parallel study was conducted with 13 healthy volunteers. In the control phase, after an overnight fast, each subject received a single dose of 2 mg pitavastatin. After a 1-week washout period, in the UDCA phase, subjects received a daily oral dose of 600 mg of UDCA (300 mg b.i.d.) for 14 days. On day 15, 2 mg of pitavastatin was administered as described previously for the control phase. Results: In the UDCA phase, the maximum plasma concentration (Cmax) of pitavastatin was slightly higher than in the control phase (48.6 ± 22.9 ng/mL vs. 42.4 ± 16.1 ng/mL). However, the overall pharmacokinetic parameters of pitavastatin and pitavastatin lactone during the two study phases were not significantly different. Conclusions: UDCA had no significant effect on the pharmacokinetics of pitavastatin. These results do not support the notion that UDCA increases the systemic exposure of OATP1B1 substrate by inhibiting HNF1α and decreasing OATP1B1 transporter expression.Correspondence to:
Seok-Yong Lee, PhD
School of Pharmacy, Sungkyunkwan University
Suwon 440-746, Republic of Korea
Email: [email protected]
Original
Paeonol inhibited TNF-α-induced GM-CSF expression in fibroblast-like synoviocytes
Yan Li, Pin Li, Shu-huan Lin, Yi-qing Zheng, and Xiang-xiong Zheng
Price
42.00 $
Page No. 986
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (986-995)
Paeonol inhibited TNF-α-induced GM-CSF expression in fibroblast-like synoviocytes
Yan Li1,2, Pin Li2, Shu-huan Lin1,2, Yi-qing Zheng1,2, and Xiang-xiong Zheng1,2
1Department of Rheumatology, Union Hospital of Fujian Medical University, Fuzhou, and 2Fujian Institute of Clinical Immunology, Union Hospital of Fujian Medical University, Fuzhou, China
Objectives: Granulocyte macrophage colony-stimulating factor (GM-CSF) has been proved to be among the most important chemokines, playing a key role in rheumatoid arthritis (RA). However, the mechanism underlying the regulation of GM-CSF has not been established clearly yet. The aim of this study was to investigate the influence of paeonol in the expression of GM-CSF in fibroblast-like synoviocytes (FLS). Methods: The expression of GM-CSF was detected both at protein and mRNA levels in FLS after the stimulation of TNF-α at diverse concentrations and times. And then GM-CSF was detected again after pre-treatment with paeonol. Phosphorylation of PI3K/Akt and expression of NF-κB and p-IκBα were detected with western blot. Meanwhile, inhibitors of the pathways were used to investigate the mechanism of regulation of GM-CSF. Results: Recombinant TNF-α up-regulated GM-CSF in a concentration- and time-dependent manner in FLS, which was significantly suppressed by paeonol. Paeonol also exerted its ability to suppress the promoting effects of TNF-α on the phosphorylation of PI3K/Akt and activation of NF-κB pathway. Administration of the inhibitors LY294002, perifosine, BAY11-7082, and SC-514 confirmed the roles of PI3K/Akt and NF-κB on the production of GM-CSF. Furthermore, TNF-α induced proliferation, while paeonol suppressed proliferation of FLS. Conclusion: These results demonstrate that paeonol suppressed TNF-α-induced GM-CSF production via the PI3K/Akt/NF-κB pathway.Correspondence to:
Dr. Xiang-xiong Zheng, MD
Department of Rheumatology
Union Hospital of Fujian Medical University
29 Xinquan Road, Fuzhou, 350001, PR China
Email: [email protected]
Original
Effect of oral siponimod (BAF312) on the pharmacokinetics and pharmacodynamics of a monophasic oral contraceptive in healthy female subjects
Shibadas Biswal, Uday Kiran Veldandi, Caroline Derne, GangaRaju Golla, Naguib Muhsen, and Eric Legangneux
Price
42.00 $
Page No. 996
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (996-1004)
Effect of oral siponimod (BAF312) on the pharmacokinetics and pharmacodynamics of a monophasic oral contraceptive in healthy female subjects
Shibadas Biswal1, Uday Kiran Veldandi1, Caroline Derne2, GangaRaju Golla1, Naguib Muhsen3, and Eric Legangneux2
1Novartis Healthcare Private Limited, Hyderabad, India, 2Novartis Pharma AG, Basel, Switzerland, and 3QPS Netherlands B.V., Groningen, The Netherlands
Objective: To evaluate the effects of siponimod (BAF312) on the pharmacokinetics (PK) and pharmacodynamics (PD) of a monophasic oral contraceptive (OC). Materials and methods: This was a phase 1, single-center, open-label, multipledose, single-sequence study in healthy females. Eligible subjects (n = 23) were exposed sequentially to two treatment periods: period 1 (OC alone) and period 2 (OC + siponimod) in two consecutive menstrual periods. PK parameters were assessed on day 21 of both treatment periods. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone concentrations were measured at baseline and days 3, 6, 8, 11, 14, 16, 19, 21, and 23 of each period. Largest ovarian follicle size and sex hormone-binding globulin (SHBG) concentration were measured and Hoogland score was calculated at baseline and day 21 of each period. Safety and tolerability of siponimod was also assessed. Results: Co-administration (OC + siponimod) increased the AUCτ,ss and Cmax,ss of levonorgestrel by 28% and 18%, respectively, but had no effect on the PK of ethinylestradiol. No significant changes in estradiol, FSH, and LH were noted with co-administration vs. OC alone. Progesterone levels < 5 nmol/L, largest follicle size < 10 mm, and Hoogland score of 1 on day 21 indicated lack of ovulation in all subjects during co-administration. Co-administration was well tolerated. Conclusion: In conclusion, PK and PD of the OC were not altered to a clinically significant extent and contraceptive efficacy was maintained with co-administration. Hence, OC as a contraceptive measure can be safely co-administered with siponimod.Correspondence to:
Shibadas Biswal, MD
Novartis Healthcare Pvt. Ltd.
Raheja Mind Space, Hitech City,
Madhapur, Hyderabad, 500 081, India
Email: [email protected]
Original
The effect of voglibose on the pharmacokinetics of metformin in healthy Korean subjects
Ho-Sook Kim, Minkyung Oh, Eun Ji Kim, Geun Seog Song, Jong-Lyul Ghim, Ji-Hong Shon, Dong-Hyun Kim, and Jae-Gook Shin
Price
42.00 $
Page No. 1005
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (1005-1011)
Effect of voglibose on the pharmacokinetics of metformin in healthy Korean subjects
Ho-Sook Kim1,2, Minkyung Oh1, Eun Ji Kim3, Geun Seog Song3, Jong-Lyul Ghim2, Ji-Hong Shon1,2, Dong-Hyun Kim1, and Jae-Gook Shin1,2
1Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, 2Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, and 3Pharmaceutical BU, CJ Cheiljedang Corp., Seoul, Republic of Korea
Objective: The objective of this study was to evaluate the effects of voglibose on the pharmacokinetics of metformin. Methods: A randomized, open-label, two-way crossover study with a 7-day washout period was conducted. All subjects were given an oral dose of metformin with or without voglibose 3 × daily for 7 days. Plasma concentrations of metformin on day 7 were measured using high performance liquid chromatography (HPLC) with UV detection for pharmacokinetic assessment Vital signs and adverse events were monitored, and physical examinations and laboratory tests were conducted to evaluate safety. Results: 22 subjects completed the study. The geometric mean ratios for Css,max of metformin (metformin plus voglibose vs. metformin only) were 0.98 (90% CI, 0.92 – 1.05; p > 0.05) and for AUCτ, the ratio was 0.99 (90% CI, 0.92 – 1.06; p > 0.05). There were no significant differences in adverse drug reactions between metformin with and without voglibose. However, the incidence of adverse events was higher in period 1 than in period 2 (16 cases vs. 1 case, p < 0.001). Conclusions: Co-administration of metformin and voglibose had no statistically or clinically significant effects on the pharmacokinetics of metformin in healthy subjects. The pharmacodynamic interaction study to evaluate the effect of metformin on the pharmacodynamics of voglibose is in progress.Correspondence to:
Jae-Gook Shin, MD, PhD
Department of Pharmacology and Clinical Pharmacology
Inje University College of Medicine and Busan Paik Hospital
633-165 Gaegum-dong, Jin-gu, Busan 614-735, Korea
Email: [email protected]
Case Report
Occult interferon α-induced pulmonary granulomatosis despite continuation of treatment
Jens Schreiber, Susann Langwieler, Sandra Riedel, Kerstin Stein, and Peter Malfertheiner
Price
42.00 $
Page No. 1012
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 11/2014 (1012-1016)
Occult interferon α-induced pulmonary granulomatosis despite continuation of treatment
Jens Schreiber1, Susann Langwieler1, Sandra Riedel1, Kerstin Stein2, and Peter Malfertheiner2
1Department of Pulmonology, and 2Department of Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke-University Magdeburg, University Hospital, Magdeburg, Germany
Interferon α (IFNα)-based treatment of chronic hepatitis C viral (HCV) infection may induce pulmonary and extrapulmonary sarcoidosis. We report a case of a 50-year-old male patient who suffered from hepatitis C-induced liver cirrhosis with respiratory insufficiency due to severe hepatopulmonary syndrome. After 9 months of treatment with IFNα and ribavirin, he developed an asymptomatic, clinically occult pulmonary granulomatosis, which was not detectable in CT. The diagnosis was made by bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy. The condition did not progress to clinically apparent disease despite continuation of IFNα treatment.Correspondence to:
Prof. Dr. med. Jens Schreiber
University Hospital Magdeburg
Department of Pulmonology
Leipziger Str. 44, 39120 Magdeburg, Germany
Email: [email protected]
