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

Mov Disord. 1995 Jul;10(4):433-9. doi: 10.1002/mds.870100405.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • 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

Substances

  • Antiparkinson Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Suppositories
  • Levodopa
  • Apomorphine