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.

Dual catheter technique for the treatment of severe coronary artery perforations

“…The first 5 μL of the filtrates was discarded and the subsequent filtrates were collected. Then, an appropriate amount of the filtrate was diluted with acetonitrile and assayed by a validated HPLC with mass spectrometry (MS) detection method,29 details are described later.…”

Improving Biopharmaceutical Properties of Vinpocetine Through Cocrystallization

“…All the volunteers were prohibited to take medicines, following a one week wash out period before the beginning of the present study. In this study, apovincaminic acid plasma concentrations were monitored, as suggested in the literature 34 . This choice was made in consideration of the fast metabolic conversion from vinpocetine to apovincaminic acid.…”

“…The determination of apovincaminic acid concentration was performed using a previously published HPLC method 34 . The preparation of the samples for HPLC analysis was performed according to the method reported by Hasa et al 33 .…”

Studies on Pharmacokinetic Drug Interaction Potential of Vinpocetine

“…Non-competitive inhibition of dextromethorphan metabolism (mediated by CYP2D6) was seen with a K i value of 26 µM ( Figure 4 ). It should also be noted that vinpocetine has been shown to have a very low oral bioavailability (6%) in humans with maximum plasma concentration (Cmax) value of 60 ng/mL [ 27 ]. Hence, it is highly unlikely that the inhibitory concentrations (IC 50 and K i ) observed in this study will be achieved in vivo to inhibit CYP3A4 and CYP2D6 and thus the possibility of CYP mediated drug interaction seems to be remote.…”