Oral absorption profile of nitrendipine in healthy subjects: a kinetic and dynamic study.
1. In nine healthy male subjects the kinetics of nitrendipine were assessed after i.v. administration and its absorption profile was studied when given by a tablet formulation and by an osmotic pumping device (Osmet) with a zero-order in vitro release of 2.62 +/- 0.19 mg h-1 for 13 h. 2. Plasma concentrations of nitrendipine and its pyridine metabolite, heart rate and blood pressure were determined at regular intervals after drug administration. 3. After i.v. nitrendipine, the plasma concentration declined triexponentially with a mean terminal elimination half-life of 11.7 +/- 5.4 h. The mean systemic plasma clearance was 1.47 +/- 0.22 l min-1. 4. Administration of the Osmet resulted in a relatively smooth plasma concentration-time profile in comparison with the tablet. The mean plateau concentration was 2.63 +/- 1.31 ng ml-1 and the duration of this plateau was 10.7 +/- 3.2 h. The intake of food gave rise to a transient increase of the plasma concentration of both nitrendipine and its pyridine metabolite. 5. The mean bioavailability of nitrendipine from the Osmet (8.2 +/- 1.6%) was lower than from the tablet (11.1 +/- 4.5%), which is probably due to release of nitrendipine in lower parts of the G.I. tract where absorption is not or less possible. 6. Intravenous administration caused a transient decrease in DBP of 26 +/- 4%, accompanied by a maximal reflex tachycardia of 46 +/- 17%. No clear haemodynamic effects were observed after oral administration. The Osmet produced less side-effects (headache) than the tablet.
Soons
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PA
Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
de Boer
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AG
van Brummelen
P
P
Breimer
D D
DD
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D009568:Nitrendipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011897:Random Allocation; D013607:Tablets
D013607:Tablets; D009568:Nitrendipine