PMID- 31232274
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20211204
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 57
IP  - 8
DP  - 2019 Aug
TI  - Investigation of bioequivalence, safety, and tolerability of a fixed-dose 
      combination of nifedipine GITS and candesartan compared with the corresponding 
      loose-dose combination under fed conditions
.
PG  - 420-428
LID - 10.5414/CP203200 [doi]
AB  - OBJECTIVE: To investigate the bioequivalence, safety, and tolerability of 
      single-dose nifedipine gastrointestinal therapeutic system (GITS) and candesartan 
      as a fixed-dose combination (FDC) relative to the loose combination in healthy 
      males under fed conditions. MATERIALS AND METHODS: A total of 48 subjects 
      received nifedipine GITS 60 mg and candesartan 32 mg as an FDC or loose 
      combination in an open-label, 2-way crossover, 2-treatment sequence design, with 
      a washout of at least 5 days between treatments. Study medications were 
      administered following an overnight fast of at least 10 hours, and 30 minutes 
      after ingestion of a high-fat test meal. Plasma samples were collected at 
      intervals over a 48-hour period post-dosing. Safety and tolerability parameters 
      were documented throughout the study. RESULTS: For nifedipine, 90% confidence 
      intervals (CIs) for the ratios of FDC/loose combination were within acceptance 
      limits of bioequivalence (i.e., 80 - 125%) for both AUC(0-tlast) (91.36%; 111.5%) 
      and C(max) (87.93%; 100.5%). For candesartan, 90% CIs for the ratios of FDC/loose 
      combination were within acceptance limits for AUC(0-tlast) (112.8%; 124.4%), but 
      not for C(max) (120.5%; 137.8%). There were no serious adverse events (AEs) or 
      AEs leading to treatment discontinuation and no clinically relevant changes in 
      vital signs or laboratory parameters. CONCLUSION: A single dose of the 
      FDC-containing nifedipine GITS 60 mg and candesartan 32 mg, when compared to the 
      corresponding loose combination under fed conditions, met the criterion for 
      bioequivalence based on AUC(0-tlast), while the slightly higher C(max) for 
      candesartan is not considered clinically relevant. The FDC displayed safety and 
      tolerability profiles similar to the loose combination.
FAU - Thomas, Dirk
AU  - Thomas D
FAU - Liu, Yuwang
AU  - Liu Y
FAU - Stein, Herbert
AU  - Stein H
FAU - Weimann, Boris
AU  - Weimann B
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Drug Combinations)
RN  - 0 (Tablets)
RN  - 0 (Tetrazoles)
RN  - I9ZF7L6G2L (Nifedipine)
RN  - S8Q36MD2XX (candesartan)
MH  - Area Under Curve
MH  - Benzimidazoles/*administration & dosage
MH  - Biphenyl Compounds
MH  - Cross-Over Studies
MH  - Drug Combinations
MH  - Humans
MH  - Male
MH  - Nifedipine/*administration & dosage
MH  - Tablets
MH  - Tetrazoles/*administration & dosage
MH  - Therapeutic Equivalency
EDAT- 2019/06/25 06:00
MHDA- 2019/08/06 06:00
CRDT- 2019/06/25 06:00
PHST- 2019/07/17 00:00 [accepted]
PHST- 2019/06/25 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2019/06/25 06:00 [entrez]
AID - 185270 [pii]
AID - 10.5414/CP203200 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2019 Aug;57(8):420-428. doi: 10.5414/CP203200.