Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers

• Published in: Drug design, development and therapy development and therapy, 2017-01, Vol.11, p.3543-3550
• Main Authors: Oh, Minkyung, Park, Sung-Eun, Ghim, Jong-Lyul, Choi, Young-Kyung, Shim, Eon-Jeong, Shin, Jae-Gook, Kim, Eun-Young
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Amlodipine; Amlodipine - administration & dosage; Amlodipine - pharmacokinetics; Benzimidazoles - administration & dosage; Benzimidazoles - pharmacokinetics; Benzoates - administration & dosage; Benzoates - pharmacokinetics; Bioavailability; Bioequivalence; Blood pressure; Cardiovascular disease; Clinical trials; Comparative analysis; Cross-Over Studies; Diuretics; Dosage and administration; Dose-Response Relationship, Drug; Drug development; Drug dosages; Drugs; Family medical history; fixed-dose combination; Genomics; Headache; Health aspects; Health risk assessment; Healthy Volunteers; Hospitals; Humans; Hypertension; Laboratories; Laboratory tests; Liquid chromatography; Male; Males; Mass spectrometry; Mass spectroscopy; Maximum Tolerated Dose; Metabolism; Middle Aged; Original Research; Pharmaceuticals; Pharmacokinetics; Pharmacology; Physical examinations; S-amlodipine; Safety; Safety and security measures; Statistical methods; Tablets - administration & dosage; Tablets - pharmacokinetics; Task forces; Telmisartan; Young Adult
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S148534

This study compared the pharmacokinetic (PK) and safety profiles of a fixed-dose combination (FDC) formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs. This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration-time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews. The geometric mean ratios and 90% CIs for the maximum plasma concentration (C ) and area under the curve from time zero to the last sampling time (AUC ) were 0.8782 (0.8167-0.9444) and 0.9662 (0.9210-1.0136) for telmisartan and 1.0069 (0.9723-1.0427) and 1.0324 (0.9969-1.0690) for S-amlodipine, respectively. A total of 36 adverse events (AEs) were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting. For both telmisartan and S-amlodipine, the C and AUC 90% CIs were between ln (0.8) and ln (1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile to the coadministration of these drugs.