STEADY-STATE PHARMACOKINETIC PROPERTIES OF PRAMIPEXOLE IN HEALTHY-VOLUNTEERS

Pramipexole is a dopamine receptor agonist that has proved effective i n the treatment of Parkinson's disease. The pharmacokinetic properties of pramipexole at steady-state concentrations were studied in 16 heal thy men and women at four dose levels throughout the range recommended for Parkinson's patients. Plasma and urine samples collected within t he four dose intervals were assayed for concentrations of pramipexole, using high-performance liquid chromatography. The total oral clearanc e for all participants was 419 mL/min. The mean volume of distribution and elimination half-life for all participants was 486 +/- 93.2 L and 12.9 +/- 3.27 hours. Concentrations of pramipexole were proportional to dose, although the drug's pharmacokinetic properties differed betwe en men and women. The area under the concentration-time curve for each dose level was 35% to 43% greater in women, mainly because of a 24% t o 27% lower oral clearance. The mean creatinine clearance in men and w omen was 132 +/- 12.8 mL/min/1.73 m(2) and 80.9 +/- 15.6 mL/min/1.73 m (2), respectively. The renal clearance of pramipexole accounts for app roximately 80% of oral clearance, and there was a significant correlat ion between renal and creatinine clearances. The influence of gender c ould not be distinguished from the influence of age and the resulting reduced creatinine clearance, but the measurement of pharmacokinetic p roperties produced linear results in both men and women.