Evolution of the bioavailability and other pharmacokinetic parameters of levodopa (with carbidopa) in rabbits

Levodopa pharmacokinetics show important inter- and intraindividual differences when it is administered by the oral route. As a result of fluctuating drug plasma concentrations, patients may develop motor fluctuations and dyskinesias. Therefore, it is important to perform studies on levodopa pharmacokinetics in the same individual. The aim of this study was to contribute to a better knowledge of the evolution of the pharmacokinetics of levodopa administered with carbidopa. The study involved the oral administration of 20/5 mg/kg levodopa/carbidopa to rabbits 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 treatment, the levodopa AUC increased by 12.6% from day 1 (range: 114.2-150.7 microg.min/ml) to day 7 (range: 131.1-166.0 microg.min/ml) and C(max) increased by 9.6% (range: 1.90-2.86 microg/ml on day 1 and 2.12-3.13 microg/ml on day 7). After 14 days of treatment, the increase in AUC was 17.0% (range: 119.6-160.1 microg.min/ml on day 1 and 142.9-172.7 microg.min/ml on day 14) and C(max) increased by 6.5% (range: 2.29-2.96 microg/ml on day 1 and 2.41-3.07 microg/ml on day 14). The values obtained for C(min) (sample obtained immediately before levodopa/carbidopa administration) in both groups increased progressively with the duration of the treatment. C(max) and AUC values were very similar after 7 or 14 days of treatment. The time needed for C(min) stabilization was slightly higher, because we found significant differences until day 11 of treatment.