Steady-state pharmacokinetic properties of pramipexole in healthy volunteers.
Pramipexole is a dopamine receptor agonist that has proved effective in the treatment of Parkinson's disease. The pharmacokinetic properties of pramipexole at steady-state concentrations were studied in 16 healthy men and women at four dose levels throughout the range recommended for Parkinson's patients. Plasma and urine samples collected within the four dose intervals were assayed for concentrations of pramipexole, using high-performance liquid chromatography. The total oral clearance 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 between 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% to 27% lower oral clearance. The mean creatinine clearance in men and women was 112 +/- 12.8 mL/ min/1.73 m2 and 80.9 +/- 15.6 mL/min/1.73 m2, respectively. The renal clearance of pramipexole accounts for approximately 80% of oral clearance, and there was a significant correlation between renal and creatinine clearances. The influence of gender could not be distinguished from the influence of age and the resulting reduced creatinine clearance, but the measurement of pharmacokinetic properties produced linear results in both men and women.
Wright
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Clinical Pharmacokinetics and CNS/Critical Care Units, Pharmacia & Upjohn Company, Kalamazoo, Michigan 49007, USA.
Sisson
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Ichhpurani
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Peters
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D000328:Adult; D000978:Antiparkinson Agents / Q000493:pharmacokinetics*; D052160:Benzothiazoles; D018491:Dopamine Agonists / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000077487:Pramipexole; D013844:Thiazoles / Q000009:adverse effects / Q000493:pharmacokinetics*
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; D013844:Thiazoles; D000077487:Pramipexole