The pharmacokinetics and metabolism of R-
apomorphine were determined in 10 patients with
idiopathic Parkinson's disease after
intravenous infusion of 30 micrograms.kg-1 in 15 min. Specifically, emphasis was on enantiomeric interconversion into S-
apomorphine and on the formation of
apocodeine and
isoapocodeine, since these metabolites may interfere with the pharmacodynamics of R-
apomorphine. The pharmacokinetics of R-
apomorphine in plasma were determined using an enantioselective high-performance liquid chromatography assay. In most patients, the plasma concentration versus time profile was characterized by a biexponential function. The values of relevant pharmacokinetic parameters were as follows: clearance 40 +/- 15 ml.min-1.kg-1, volume of distribution at steady state 1.6 +/- 0.5 l.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 metabolites
apocodeine and
isoapocodeine could be detected in plasma. The metabolism of
apomorphine was characterized on basis of the excretion of unchanged R-
apomorphine, S-
apomorphine,
apocodeine,
isoapocodeine, and their 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 unchanged
apomorphine,
apomorphine sulfate, and
apomorphine glucuronide amounted to 0.3 +/- 0.4%, 3.8 +/- 1% and 6.0 +/- 2.2% of the administered dose, respectively. The findings of this study show that on
intravenous administration, S-
apomorphine and the metabolites
apocodeine and
isoapocodeine are unlikely to interfere with the
pharmacologic actions 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.