title: Pharmacokinetics and comparative bioavailability of two vinpocetine tablet formulations in healthy volunteers by using the metabolite apovincaminic acid as pharmacokinetic parameter.
abstract: The objective of this study was to evaluate the pharmacokinetics of apovincaminic acid, the main metabolite of vinpocetine ((3alpha, 16alpha) -eburnamenine-14-carboxylic acid ethyl ester, CAS 42971-09-5), and to assess the average bioequivalence of two immediate release formulations of 10 mg vinpocetine tablets in 24 healthy male volunteers. The relative bioavailability of the test (generic) product (Vimpocetina) with respect to the reference product was determined in a single dose, randomized, crossover study. A simple, rapid specific and reliable high performance liquid chromatographic method coupled with mass spectrometry detection has been developed and validated for vinpocetine and apovincaminic acid. However, only the concentrations of the metabolite could be used for bioequivalence determinations because the concentrations of the parent drug were too low to be accurately measured in the biological matrix. The compartmental analysis of the metabolite's appearance-disappearance in blood shows similarity with first-order kinetics of a drug extravascularly administered. The apparent pharmacokinetic constants were determined. The mean values for the Cmax were 49.5 (+/- 16) ng/ml for test and 51.4 (+/- 14) ng/ml for the reference product. The mean values for the AUC0-infinity were 95 (+/- 29) ng/ml x h for test and 96.9 (+/- 26) ng/ml x h for reference, respectively. The 90 % confidence intervals for test/reference mean ratios of the plasma pharmacokinetic variables Cmax and AUC0-infinity lie between 0.83-1.08 and 0.88-1.08, respectively, which is within the conventional bioequivalence range of 80-125 % (Schuirman test). The difference between Tmax of the test and reference products was statistically non-significant (Friedman test). The test product is therefore bioequivalent to the reference product with respect to the rate and extent of apovincaminic acid pharmacokinetics.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy Iuliu Hatieganu Cluj-Napoca, Romania. vlaselaur@yahoo.com
authors.forename: Laurian
authors.initials: L
authors.lastname: Vlase
authors.forename: Bogdan
authors.initials: B
authors.lastname: Bodiu
authors.forename: Sorin E
authors.initials: SE
authors.lastname: Leucuta
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D008297:Male; D013607:Tablets; D013810:Therapeutic Equivalency; D014748:Vinca Alkaloids / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D013607:Tablets; D014748:Vinca Alkaloids; C032858:apovincaminic acid; C013983:vinpocetine