Sook Jin Seong1, Mi-Sun Lim2, Joomi Lee1, Boram Ohk1, Mi-Ri Gwon1, Bo Kyung Kim1, Hyun-Ju Kim1, Dong Heon Yang3, Hae Won Lee1, Woo Youl Kang1, Young-Ran Yoon4. 1. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Cell and Matrix Research Institute and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu, Republic of Korea. 2. College of Pharmacy, Yeungnam University, Kyungsan, Kyungpook, Republic of Korea. 3. Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea. 4. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Cell and Matrix Research Institute and Clinical Trial Center, Kyungpook National University Graduate School and Hospital, Daegu, Republic of Korea. yry@knu.ac.kr.
Abstract
BACKGROUND AND OBJECTIVE: Combination therapy is recommended for the effective management of hypertension according to most treatment guidelines, including those of the US Joint National Committee. Therefore, pharmacokinetic drug interactions are an important issue in combination therapy for hypertension. In this study, the pharmacokinetic properties of telmisartan and chlorthalidone were evaluated to investigate their pharmacokinetic interactions in healthy subjects. METHODS: Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted. In study A, 43 participants received80 mg of telmisartan orally for 7 days, and were then administered oral chlorthalidone 25 mg for 14 days (days 8-21), coadministered with 80 mg of telmisartan from day 15. In study B, 14 participants receivedoral chlorthalidone (25 mg) for 13 days, followed by coadministration with 80 mg of telmisartan orally for 7 days. RESULTS: The geometric mean ratios (GMRs) (90 % confidence intervals [CIs]) of the maximum plasma concentration (C max,ss) and area under the concentration-time curve for the dosing interval at steady state (AUCτ,ss) of telmisartan (with and without chlorthalidone) were 1.018 (0.861-1.203) and 1.099 (1.015-1.190), respectively. For chlorthalidone (with/without telmisartan), the GMRs (90 % CIs) for C max,ss and AUCτ,ss were 0.996 (0.922-1.075) and 0.992 (0.925-1.064), respectively. The GMRs and 90 % CIs for telmisartan and chlorthalidone were all within the 0.80-1.25 range. CONCLUSION: Thus, in this study, there was no significant pharmacokinetic interaction between telmisartan and chlorthalidone. CLINICALTRIAL. GOV IDENTIFIER: NCT01806363.
RCT Entities:
BACKGROUND AND OBJECTIVE: Combination therapy is recommended for the effective management of hypertension according to most treatment guidelines, including those of the US Joint National Committee. Therefore, pharmacokinetic drug interactions are an important issue in combination therapy for hypertension. In this study, the pharmacokinetic properties of telmisartan and chlorthalidone were evaluated to investigate their pharmacokinetic interactions in healthy subjects. METHODS: Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted. In study A, 43 participants received 80 mg of telmisartan orally for 7 days, and were then administered oral chlorthalidone 25 mg for 14 days (days 8-21), coadministered with 80 mg of telmisartan from day 15. In study B, 14 participants received oral chlorthalidone (25 mg) for 13 days, followed by coadministration with 80 mg of telmisartan orally for 7 days. RESULTS: The geometric mean ratios (GMRs) (90 % confidence intervals [CIs]) of the maximum plasma concentration (C max,ss) and area under the concentration-time curve for the dosing interval at steady state (AUCτ,ss) of telmisartan (with and without chlorthalidone) were 1.018 (0.861-1.203) and 1.099 (1.015-1.190), respectively. For chlorthalidone (with/without telmisartan), the GMRs (90 % CIs) for C max,ss and AUCτ,ss were 0.996 (0.922-1.075) and 0.992 (0.925-1.064), respectively. The GMRs and 90 % CIs for telmisartan and chlorthalidone were all within the 0.80-1.25 range. CONCLUSION: Thus, in this study, there was no significant pharmacokinetic interaction between telmisartan and chlorthalidone. CLINICALTRIAL. GOV IDENTIFIER: NCT01806363.
Authors: J Stangier; C A Su; M G Hendriks; J J van Lier; F A Sollie; B Oosterhuis; J H Jonkman Journal: J Clin Pharmacol Date: 2000-12 Impact factor: 3.126
Authors: Domenic Sica; George L Bakris; William B White; Michael A Weber; William C Cushman; Patrick Huang; Andrew Roberts; Stuart Kupfer Journal: J Clin Hypertens (Greenwich) Date: 2012-03-06 Impact factor: 3.738