Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on pharmacokinetic behavior of levodopa in dogs and parkinsonian patients

Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on... The relationship between the dose of levodopa and its pharmacokinetic behavior following intravenous and oral administration was investigated in dogs and parkinsonian patients. Six beagle dogs received single doses of 2.4, 4.8, and 9.6 mg of levodopa/kg iv and single doses of 4.8, 9.6, and 19.2 mg of levodopa/kg po in a crossover fashion on separate occasions. Three parkinsonian patients received single oral doses of ∼3.8, 7.7, and 15.4 mg of levodopa/kg in a crossover test. Plasma samples were analyzed for intact levodopa and total dopamine. The relationship between the area under the plasma concentration–time curve (AUC) of levodopa and the intravenous dose to dogs was linear. However, in both dogs and patients, the relationship after oral dosing was nonlinear, with the relative AUC increasing with increasing dose. Therefore, the pharmacokinetic behavior of levodopa after oral administration to dogs and patients was dose dependent. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Pharmaceutical Sciences Wiley

Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on pharmacokinetic behavior of levodopa in dogs and parkinsonian patients

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Publisher
Wiley
Copyright
Copyright © 1980 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3549
eISSN
1520-6017
DOI
10.1002/jps.2600691205
Publisher site
See Article on Publisher Site

Abstract

The relationship between the dose of levodopa and its pharmacokinetic behavior following intravenous and oral administration was investigated in dogs and parkinsonian patients. Six beagle dogs received single doses of 2.4, 4.8, and 9.6 mg of levodopa/kg iv and single doses of 4.8, 9.6, and 19.2 mg of levodopa/kg po in a crossover fashion on separate occasions. Three parkinsonian patients received single oral doses of ∼3.8, 7.7, and 15.4 mg of levodopa/kg in a crossover test. Plasma samples were analyzed for intact levodopa and total dopamine. The relationship between the area under the plasma concentration–time curve (AUC) of levodopa and the intravenous dose to dogs was linear. However, in both dogs and patients, the relationship after oral dosing was nonlinear, with the relative AUC increasing with increasing dose. Therefore, the pharmacokinetic behavior of levodopa after oral administration to dogs and patients was dose dependent.

Journal

Journal of Pharmaceutical SciencesWiley

Published: Dec 1, 1980

Keywords: ; ;

References

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