Dose-dependent pharmacokinetics of laevodopa and its metabolites in the rat.
1. Plasma levels of total radioactivity, unchanged laevodopa, dopamine, 3-O-methyldopa and non-amino phenolic acids were measured in rats treated orally with [3H]laevodopa at total laevodopa doses of 1, 10, 20 and 100mg/kg while the radioactive dose was maintained at 100muCi/kg for all animal groups. 2. Within the dosage range studied, non-linear pharmacokinetics were observed for unchanged laevodopa, non-amino phenolic acids and dopamine but not for 3-O-methyldopa. 3. The area under the plasma concentration-time curve for laevodopa increased exponentially with linear increments in the oral dose. This non-linear increase in laevodopa bioavailability is consistent with the hypothesis that high oral doses of laevodopa are required to saturate gastro-intestinal metabolism of the drug. 4. At the lower doses (1 and 20 mg/kg), only 2-3% of total radioactivity could be attributed to dopamine. At 100mg/kg, the dopamine metabolite fraction amounted to about 1/3 of total radioactivity in the plasma.
D000818:Animals; D004298:Dopamine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D007980:Levodopa / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D013997:Time Factors
D007980:Levodopa; D004298:Dopamine