[Crossover pharmacokinetic study of quinupramine in 6 subjects]

The pharmacokinetic study of quinupramin was developed on healthy volunteers, after cross-over administrations of three doses (2.5 and 7.5 mg P.O. and a 2.5 mg intravenous bolus dose). A specific and sensitive Gas chromatographymass spectrometry (GC-MS) method was applied to the determination of Quinupramin in plasma and urine. The calculated kinetic data for Quinupramin indicated a good bioavailability for the oral doses (2.5 and 7.5 mg). The coefficient of bioavailability (F) was found to be (0.75), with small individual variations. After oral administration, the area under experimental points of the curves (AUC 0 leads to infinity): 43.7 +/- 10.2 (S.E.M.) and 132.5 +/- 8.3 ng.ml-1.h, respectively, were proportional to doses. Blood levels (CMAX) were about 1.1 and 3.4 ng.ml-1 at 3 hours, for oral doses of 2.5 and 7.5 mg. The pharmacokinetic of Quinupramin was not dose-dependent. The high value of the apparent volume of distribution (A.V.D.) 34.2 +/- 4.8 l.kg-1 after bolus I.V., indicated a very high distribution of Quinupramin, as for all anti-depressants in a deep compartment (CNS). The apparent terminal half life of elimination was very high: 33.5 h (+/- 2.7 S.E.M.) for 2.5 mg bolus I.V. and 28.8 h (+/- 5.01 S.E.M.), 33.1 (+/- 3.2 S.E.M.) for 2.5 mg and 7.5 mg oral doses respectively. The lack of metabolism for Quinupramin, demonstrated by many authors, explained the absence of interindividual variations of bioavailability. The renal elimination (CLr) after bolus I.V. was 2.6% of the dose, after 72 h. Many variations of plasma concentrations illustrated a predominant biliary excretion. The decline in plasma Quinupramin concentrations (Ct) was fitted to a bi-exponential equation, using least-square regression analysis, for the three formulations.