PHARMACOKINETICS AND CLINICAL EFFICACY OF RECTAL APOMORPHINE IN PATIENTS WITH PARKINSONS-DISEASE - A STUDY OF 5 DIFFERENT SUPPOSITORIES

The pharmacokinetics and clinical effects of apomorphine after rectal administration were determined in five patients with idiopathic Parkin son's disease (PD). Three different pharmaceutical formulations were t ested: a rectal solution of apomorphine (10 or 15 mg), a gelatin suppo sitory (25 and 50 mg), and a Witepsol-H15 suppository (50 and 100 mg). The pharmacokinetics of apomorphine were determined by measuring plas ma concentrations using a sensitive and specific high-performance liqu id chromatography method. The mean bioavailability varied between 14.7 % and 40.2%, which was the bioavailability until the end of clinical b enefit. 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 ene ma and 127.5 min for the Witepsol-H15 100-mg suppository. The time cou rse 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 respe ct 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 apom orphine solution. These results show that rectal administration of apo morphine may present an alternative to subcutaneous administration. Th e sustained-release properties of the Witepsol-H15 suppositories are e specially of interest in the treatment of on-off fluctuations in PD.