PMID- 24174172 OWN - NLM STAT- MEDLINE DCOM- 20140925 LR - 20151119 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 14 IP - 1 DP - 2014 Feb TI - Pharmacokinetics, tolerability, and safety of the single oral administration of AGSAV301 vs Exforge: a randomized crossover study of healthy male volunteers. PG - 63-72 LID - 10.1007/s40256-013-0051-2 [doi] AB - BACKGROUND AND OBJECTIVE: Valsartan, an angiotensin receptor blocker, is often used with calcium channel blockers (CCBs) such as amlodipine to control hypertension. Recently, the fixed-dose combination (FDC) of amlodipine 10 mg/valsartan 160 mg (Exforge) was approved. Amlodipine is a racemic mixture of CCB; S-amlodipine has higher activity than R-form. Therefore, AGSAV301, the FDC of S-amlodipine 5 mg/valsartan 160 mg was recently developed. The objective of this study was to compare the pharmacokinetic (PK) characteristics of S-amlodipine and valsartan when administered as one tablet each of Exforge and AGSAV301 to healthy male subjects. METHODS: This was a single-dose, randomized, open-label, two-way, two-period crossover study. Each subject received a single dose of AGSAV301 and Exforge, separated by a 3-week washout period. Plasma samples for the PK analysis of valsartan and S-amlodipine were collected at predose (0) and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, and 168 h after administration. Tolerability was also evaluated. RESULTS: A total of 29 subjects were enrolled; 24 completed this study. The S-amlodipine maximum plasma concentration (C max) geometric mean ratio (GMR) between AGSAV301 and Exforge was 0.951 (90 % CI 0.983-1.014), and area under the concentration-time curve from time 0 to last measured time point (AUClast) was 0.917 (90 % CI 0.861-0.976). The GMR of valsartan C max was 0.994 (90 % CI 0.918-1.076), and the AUClast was 0.927 (90 % CI 0.821-1.047). All adverse events (AEs) were resolved without sequelae; no serious AEs were reported. Two drugs showed similar tendencies to lower blood pressure in healthy subjects. CONCLUSIONS: The PK profiles of AGSAV301 and Exforge were bioequivalent. Both drugs were also well tolerated, with comparable AE profiles and similar blood pressure-lowering tendencies in healthy volunteers, suggesting equivalent therapeutic indications. FAU - Choi, Hee Youn AU - Choi HY AD - Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea. FAU - Kim, Yo Han AU - Kim YH FAU - Kim, Mi Jo AU - Kim MJ FAU - Noh, Yook-Hwan AU - Noh YH FAU - Lee, Shi Hyang AU - Lee SH FAU - Bae, Kyun-Seop AU - Bae KS FAU - Lim, Hyeong-Seok AU - Lim HS LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Amlodipine, Valsartan Drug Combination) RN - 0 (Antihypertensive Agents) RN - 0 (Drug Combinations) RN - 0 (Tablets) RN - 0 (Tetrazoles) RN - 1J444QC288 (Amlodipine) SB - IM MH - Administration, Oral MH - Adult MH - Amlodipine/*administration & dosage/adverse effects/pharmacokinetics MH - Amlodipine, Valsartan Drug Combination MH - Antihypertensive Agents/*administration & dosage/adverse effects/pharmacokinetics MH - Area Under Curve MH - Blood Pressure/*drug effects MH - Cross-Over Studies MH - Drug Combinations MH - Follow-Up Studies MH - Humans MH - Male MH - Stereoisomerism MH - Tablets MH - Tetrazoles/*administration & dosage/adverse effects/pharmacokinetics MH - Therapeutic Equivalency MH - Time Factors MH - Young Adult EDAT- 2013/11/01 06:00 MHDA- 2014/09/26 06:00 CRDT- 2013/11/01 06:00 PHST- 2013/11/01 06:00 [entrez] PHST- 2013/11/01 06:00 [pubmed] PHST- 2014/09/26 06:00 [medline] AID - 10.1007/s40256-013-0051-2 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2014 Feb;14(1):63-72. doi: 10.1007/s40256-013-0051-2.