Pharmacokinetics and clinical efficacy of rectal apomorphine in patients with Parkinson's disease: a study of five different suppositories.
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.
van Laar
T
T
Department of Neurology, Leiden University Hospital, The Netherlands.
Jansen
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EN
Neef
C
C
Danhof
M
M
Roos
R A
RA
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001058:Apomorphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy*; D013488:Suppositories; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013488:Suppositories; D007980:Levodopa; D001058:Apomorphine