PHARMACOKINETICS, ENANTIOMER INTERCONVERSION, AND METABOLISM OF R-APOMORPHINE IN PATIENTS WITH IDIOPATHIC PARKINSONS-DISEASE

The pharmacokinetics and metabolism of R-apomorphine were determined i n 10 patients with idiopathic Parkinson's disease after intravenous in fusion of 30 mu g.kg(-1) in 15 min. Specifically, emphasis was on enan tiomeric interconversion into S-apomorphine and on the formation of ap ocodeine and isoapocodeine, since these metabolites may interfere with the pharmacodynamics of R-apomorphine. The pharmacokinetics of R-apom orphine in plasma were determined using an enantioselective highperfor mance liquid chromatography assay. In most patients, the plasma concen tration versus time profile was characterized by a biexponential funct ion. The values of relevant pharmacokinetic parameters were as follows : clearance 40 +/- 15 ml.min(-1).kg(-1), volume of distribution at ste ady state 1.6 +/- 0.5 1.kg(-1), and terminal half-life 41 +/- 13 min. No measurable concentrations of S-apomorphine were detected in plasma, indicating that enantiomeric interconversion does not occur in vivo. Furthermore, no measurable concentrations of the methylated metabolite s apocodeine and isoapocodeine could be detected in plasma. The metabo lism of apomorphine was characterized on basis of the excretion of unc hanged R-apomorphine, S-apomorphine, apocodeine, isoapocodeine, and th eir respective sulfate and glucuronide conjugates in urine. The total excretion of unconjugated S-apomorphine, apocodeine, and isoapocodeine was less than 0.1% of the administered dose. The total excretion of u nchanged apomorphine, apomorphine sulfate, and apomorphine glucuronide amounted to 0.3 +/- 0.4%, 3.8 +/- 1.% and 6.0 +/- 2.2% of the adminis tered dose, respectively. The findings of this study show that on intr avenous administration, S-apomorphine and the metabolites apocodeine a nd isoapocodeine are unlikely to interfere with the pharmacologic acti ons of R-apomorphine in patients with idiopathic Parkinson's disease. Furthermore, no pharmacokinetic interaction between R-apomorphine and catechol-O-methyl transferase inhibitors is expected.