Comparative Bioavailability: Two Pramipexole Formulations in Healthy Volunteers after a Single Dose Administration under Fasting Conditions

Abstract

The study was performed to compare the bioavailability of two Pramipexole 0.125 mg tablet formulations: the test formulation was pramipezan ® (pramipexole) manufactured by Cobalt Pharmaceuticals, Canada/ Arrow Farmacêutica Ltda * . Sifrol ® (Pramipexole) from Boehringer Ingelheim do Brasil Química e Farmacêutica Ltda was used as reference formulation. The study was conducted open with randomized two period crossover design and 8 days wash out period in 48 volunteers of both sexes. Plasma samples were obtained over a 48 hour interval. Pramipexole was analyzed by LC-MS-MS in the presence of Tansulosina as internal standard. The mean ratio of parameters C max and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the bioequivalence. The means AUC 0-t for test and reference formulation were 8201.90 pg.h/mL and 7891.56 pg.h/mL, for AUC 0-∞ were 8574.71 pg.h/mL and 8288.01 pg.h/mL and, for C max 642.09 pg/mL and 633.94 pg/mL, respectively. Geometric mean of pramipezan ® (pramipexole) /Sifrol ® 0.125 mg individual percent ratio was 103.61% AUC 0-t , 103.13% for AUC 0-∞ and 100.81% for C max . The 90% confidence intervals were 98.02 -109.51%, 97.95 -108.59%, 93.06 -109.21%, respectively. Since the 90% confidence intervals for C max , AUC 0-t and AUC 0-∞ were within the 80 -125% interval proposed by Food and Drug Administration, it was concluded that Pramipezan ® (pramipexole) 0.125 mg tablet was bioequivalent to Sifrol ® 0.125 mg tablet according to both the rate and extent of absorption.

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

“…Based on that CV, the use of 22 subjects was adequate to draw a statistical conclusion with the power of no less than 90%. The intra-subject CV of pramipexole obtained from this study was approximately similar to those found in the literature [11,18,19]. …”

“…Using the intra-subject CV of pramipexole from the literature [11], the sample size was estimated by means of confidence intervals (CIs) as tabulated by Diletti et al [17]. There were only 23 subjects who were finally enrolled in the study.…”

“…Our current study on pramipexole was carried out with the same requirements in mind. Although similar bioequivalence studies on different formulations of pramipexole have been conducted [11,18,19], the present study still needed to be executed since the result of one bioequivalence study is specific only for one particular product and cannot be extrapolated or generalized for other generic products of the same active substance.…”

“…The number of subjects needed for this study was initially estimated to be 26 subjects, based on the intra-subject coefficient of variance (CV) of pramipexole obtained from the literature [11]. At the end of the study, the required minimum number of subjects was recalculated based on the actual CV obtained from this study, in order to meet the statistical power of 80%.…”

Comparation of Bioavailability: Two Dexlansoprazole Formulations in Beagle Dogs after a Single Dose Administration

“…Washout period was adequate and there was no quantifiable concentration of the drugs in the second period of the study, indicating that there was no carryover effect from the first to the second period. The mean ratio of parameters C max and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the bioequivalence [24].…”