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A Dose-Dependent Pharmacokinetic Study of Levodopa by Intramuscular Administration in Rabbits
| 發布日期:2008-08-05 | 維護日期:2023-03-08 發布單位:

A Dose-Dependent Pharmacokinetic Study of Levodopa by Intramuscular Administration in Rabbits

LI-HSUAN WANG1, KUANG-YANG HSU2, FENG-LIN HSU3 AND SHWU-JIUAN LIN1*

1. Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan (R.O.C.)
2. Department of Pharmaceutics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan (R.O.C.)
3. Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan (R.O.C)

(Received: January 8, 2008; Accepted: March 20, 2008)

ABSTRACT

   The dose-dependent pharmacokinetics of levodopa (L-dopa) was studied in rabbits by intramuscular administration.  Three different doses of L-dopa/carbidopa (2/0.5, 5/1.25, and 10/2.5 mg/kg) were administered to six male rabbits via an intramuscular (IM) route, and one dose of L-dopa/carbidopa (2/0.5 mg/kg) was administered via an intravenous (IV) route with a washout period of 1-week between different doses. Plasma samples were collected after each treatment and the concentrations of L-dopa and 3-O-methyldopa (an L-dopa metabolite, 3-OMD) were measured by a sensitive high-performance liquid chromatographic (HPLC) method.  Subsequently, these measurements were used to determine the pharmacokinetic behavior of L-dopa and 3-OMD.  The results indicated that the absorption of L-dopa was fast with the time to the peak within 30 min, but the formation of 3-OMD was slow with the time to the peak of 120-180 min after IM administration.  The IM bioavailability of L-dopa was in the range of 0.70-1.21, and the relative ratios of the formation of 3-OMD at different doses of L-dopa were in the range of 0.79-1.24.  No statistically significant difference could be observed for IM bioavailability of L-dopa or for the relative ratios of the formation of 3-OMD in this dose range.  The elimination half-lives of L-dopa and 3-OMD also exhibited no significant differences for each dose after IM administration.  In addition, both the area under the curve (AUC) and maximum plasma concentration (Cmax) values of L-dopa and 3-OMD increased proportionally over the dose range of 2/0.5-10/2.5 mg/kg for L-dopa/carbidopa, suggesting that L-dopa and 3-OMD obeyed dose-independent pharmacokinetics.

Key words: pharmacokinetics, intramuscular, bioavailability
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