Comparative bioavailability cf two amlodipine formulation in healthy volunteers.
The present study was conducted to find out whether the bioavailability of a 10 mg amlodipine (CAS 88150-42-9) tablet (Intervask, "test") was equivalent to that that of a reference formulation ("reference"). The pharmacokinetic parameters assessed in this study were area under the serum concentration-time curve from time zero to 144 h (AUCt), area under the serum concentration-time curve from time zero to infinity (AUCinf), the peak serum concentration of the drug (Cmax), time needed to achieve the peak serum concentration (tmax), and elimination half life (t(1/2)). This was a cross-over, randomized, single-blind study which included 12 healthy male and female volunteers under fasting condition. In each of the two study periods (separated by a washout of 3 weeks) a single dose of test or reference drug was administered. Blood samples were taken up to 144 h post dose, the plasma was separated and the concentrations of amlodipine were determined by a LC/MS method. The mean AUCt, AUCinf, Cmax, and t(1/2) were 353.15 ng x h/mL, 417.86 ng x h/mL, 8.08 ng/mL, and 48.04 h, respectively, for the test drug and 359.99 ng x h x mL(-1), 408.23 ng x h/mL, 8.22 ng/mL, and 43.81 h, respectively, for the reference drug. The median Tmax of the test drug and reference drug were 8.0 h and 8.5 h, respectively. The point estimators of the ratios test/reference drug for AUCt, AUCinf, and Cmax were 96.26%, 99.48%, and 97.03%, respectively. Furthermore, the 90% confidence intervals of the mean ratio of In-transformed were 83.73-110.68% for AUCt, 81.79-120.99% for AUCinf, and 81.94-114.81% for Cmax. It can be concluded that the two amlodipine tablets (test drug and reference drug) are bioequivalent in terms of the rate and extent of absorption.
Setiawati
Effi
E
PT Equilab International, Bioavailability and Bioequivalence Laboratory, Jakarta, Indonesia. effi@equilab-int.com
Sukmayadi
Yunaidi
Danang Agung
DA
Handayani
Lucia Rat
LR
Harinanto
Gunawian
G
Santoso
Iwan Dwi
ID
Deniati
Siti Hawa
SH
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D017311:Amlodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D016037:Single-Blind Method