KINETICS AND PHARMACODYNAMIC EFFECTS OF A NOVEL PRODRUG OF N-METHYLDOPAMINE AT SINGLE-DOSE IN HEALTHY-VOLUNTEERS

Kinetics and cardiovascular effects of SIM2055 (CAS 103878-96-2), the 4-0-phosphate of N-methyldopamine (epinine), at single dose by the oral route were studied in 9 healthy adult volunteers (6 women and 3 men) ranging in age.from 22 to 39 years. SIM2055 was administered at increasing doses (from 100 to 300 mg). Plasma concentrations of free epinine were not detectable after the 100 mg dose, but were measurable after the 200 mg and 300 mg doses. Pharmacokinetic data suggest that in man SIM2055 is promptly absorbed, quickly hydrolysed to epinine, metabolized to homovanillic acid and 3,4-dihydroxyphenylacetic acid, conjugated with sulphuric acid and excreted in large amounts into urine. The 24-h urinary recovery of the 3 metabolites considered together, expressed as a percentage of the dose of SIM2055 administered, was 78 +/- 6 with the 100 mg dose, 66 +/- 11 with the 200 mg dose and 55 +/- 6 with the 300 mg dose (mean +/- S. D.). SIM2055 was well tolerated by all subjects. After its administration, the heart rate and the systolic and diastolic blood pressure presented no systemic or clinically significant variations. No substantial changes were observed with the ECG parameters. No subject reported gastric or systemic effects during the period of observation.