PHARMACOKINETICS OF APOMORPHINE IN PARKINSONIAN-PATIENTS

Apomorphine, a dopamine agonist, has been used efficiently in parkinso nian patients to treat severe levodopa-induced on-off phenomenon. Moto r improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the underst anding of the clinical results, we studied the peripheral pharmacokine tics of apomorphine in 20 patients after intravenous (IV) or SC inject ions in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-perfo rmance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the T(max) was brief (16 +/- 11 mi n) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 +/- 25.8 min). The AUC was similar following SC and I V injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption followin g injection in the abdominal wall rather than in the thigh. In patient s chronically treated by continuous SC infusion, the apparent plasma h alf-life was five times longer than that following SC or IV injections . These pharmacokinetic data may explain the rapid onset and brief dur ation of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor res ponse obtained with continuous SC infusions.