Methods and Findings in Experimental and Clinical Pharmacology, 2008, n. 30
Levodopa pharmacokinetics show i111portanl inter- and intraindividual dijferences when it is administered by the oral route. As a result of fluctu ating drug plasma concentrations, patients may develop motor fluctuations and dyskinesias. Therefore, it is in1portanl tope1form studies on levodopa pharmacokinetics in the same individual. The aim of this sh1dy was to contribute to a better knowledge of the evolution of thephannacokinetics of lev adopa adnúnislered ivith carbidopa. The study involved the oral administration of 20/5 mg/kg levodopa/carbidopa to rahbits for two different time periods (7 or 14 days), due to the fact that inhibition of aromatic L-amino-acid decarboxylase by carbidopa is not immediate. After 7 days of treat ment, the levodopa AUC increased by 12.6%.fivm day 1 (range: 114.2-150.7 µg.min/ml) to day 7 (range: 131.1-166.0 µg.min/ml) and C"'ª" increased by 9.6% (range: 1.90-2.86 µg/ml on day 1 and 2.12-3.13 µglml on day 7). After 14 days of treatment, the increase in AUC was 17.0% (range: 119.6-160.1 µg.min/ml on day 1 and 142.9-172.7 ¡ µg.min/ml on day 14) and Cmax increased by 6.5% {tange: 2.29-2.96 µg!ml on day 1 and 2.41·-3.07
µg/ml on day 14). The values obtained for C,max (sample obtained im1nediately befare levodopa/carbidopa administration) in both grups increased progressively with the duration of the treatment. Cmax and AUC values were very similar after 7 or 14 days of treatment. The time needed far Cm,in sta bilization was slightly highe1; because we found significant djfferences until day 11 of treatment.
