Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: a study of five different suppositories

• Published in: Movement disorders Vol. 10; no. 4; p. 433
• Main Authors: van Laar, T, Jansen, E N, Neef, C, Danhof, M, Roos, R A
• Format: Journal Article
• Language: English
• Published: United States 01.07.1995
• Subjects: Aged; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - adverse effects; Antiparkinson Agents - pharmacokinetics; Apomorphine - administration & dosage; Apomorphine - adverse effects; Apomorphine - pharmacokinetics; Biological Availability; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Carriers; Drug Therapy, Combination; Exercise Test - drug effects; Female; Humans; Levodopa - adverse effects; Levodopa - therapeutic use; Male; Middle Aged; Neurologic Examination - drug effects; Parkinson Disease - blood; Parkinson Disease - drug therapy; Suppositories; Treatment Outcome
• ISSN: 0885-3185
• DOI: 10.1002/mds.870100405

The pharmacokinetics and clinical effects of apomorphine after rectal administration were determined in five patients with idiopathic Parkinson's disease (PD). Three different pharmaceutical formulations were tested: a rectal solution of apomorphine (10 or 15 mg), a gelatin suppository (25 and 50 mg), and a Witepsol-H15 suppository (50 and 100 mg). The pharmacokinetics of apomorphine were determined by measuring plasma concentrations using a sensitive and specific high-performance liquid chromatography method. The mean bioavailability varied between 14.7% and 40.2%, which was the bioavailability until the end of clinical benefit. Also, despite the differences in dose, the values of the Cmax were similar, with average values of 12.7-25.6 ng/ml. Wide differences in Tmax were observed, with values varying between 16 min for the enema and 127.5 min for the Witepsol-H15 100-mg suppository. The time course of the clinical effect was determined by assessing the time needed for walking a 25-m course and by calculating a tremor and dyskinesia score. Onset of effect was similar for each of the preparations, with an average onset time of 14-28 min. Significant differences with respect to the duration of the effect were observed. The duration of effect after administration of the Witepsol-H15 100-mg suppository was 156 +/- 43 min versus 50 +/- 13 min after rectal administration of the apomorphine solution. These results show that rectal administration of apomorphine may present an alternative to subcutaneous administration. The sustained-release properties of the Witepsol-H15 suppositories are especially of interest in the treatment of on-off fluctuations in PD.