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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 463-466 
    ISSN: 1432-1041
    Keywords: Levodopa ; Pharmacokinetics ; Parkinson's disease ; age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of age on the kinetics of a standard oral dose of levodopa administered with an inhibitor of peripheral dopa decarboxylase enzymes (benserazide) has been evaluated in 40 patients with Parkinson's disease (age 34–78 y) on chronic therapy. They were divided into 2 groups, on the basis of age below (21 patients, Group A) or above (19 patients, Group B) 65 y. The area under the plasma concentration-time curve (AUC) of levodopa was significantly greater in the older group (547 versus 428 μmol·1−1·min in Group B), coupled with a reduced apparent oral clearance (8.1 versus 10.7 ml·min−1 ·kg−1) and a longer plasma elimination half-life (67.6 versus 54.6 min). The age of the patients was positively correlated with the AUC of levodopa (r=0.474) and its plasma elimination half-life (r=0.391), and was negatively correlated with clearance (r=−0.489). The findings confirm previous data on volunteers that showed a reduction in the systemic clearance of levodopa due to age, which would probably account for the finding of a greater AUC of levodopa in older patients. The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule.
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  • 2
    ISSN: 1432-1041
    Keywords: Key words Levodopa ; Parkinson’s disease; pharmacokinetics ; pharmacodynamics ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The population pharmacokinetics and pharmacodynamics of a standardised oral test dose of levodopa have been determined in patients with mild to severe Parkinson’s disease using parametric, non-linear mixed effect modelling with the program NONMEM. Levodopa plasma concentration data and motor effect behaviour (tapping times) were obtained from 46 patients, for whom a total of 970 observations were available (approximately 21 pharmacokinetic and pharmacodynamic observations per patient). The pharmacokinetic-pharmacodynamic model used was a one-compartment first-order absorption model linked to the sigmoid EMax representation of the Hill equation via an equilibration rate-constant, ke0. The model was also tested via a reduction in the number of pharmacokinetic and pharmacodynamic data points to a total of four to eight per patient. Results: In the final regression models the Hoehn and Yahr (HY) status of the patient and duration of disease (DUR) were found to be important determinants of the pharmacodynamic parameters for levodopa. The pharmacokinetic parameters were not significantly affected by any covariates. A test group of 16 additional parkinsonian patients was used to evaluate the predictive performance of the population parameters. The predictive performance of the pharmacokinetic-pharmacodynamic modelling using the full and reduced data sets was evaluated in NONMEM using posthoc, Bayesian forecasting. Statistically insignificant bias existed among predicted and observed levodopa concentrations, whereas the pharmacodynamic model underpredicted the observed tapping times. There was little difference in the pharmacokinetic-pharmacodynamic predictive performance among results for the full and the reduced data sets. Conclusion: In a clinical setting knowledge of the population pharmacokinetic and pharmacodynamic parameters for oral levodopa may prove useful in estimating the duration of the drug’s beneficial motor activity in patients with mild to severe Parkinson’s disease (Hoehn and Yahr status I–IV).
    Type of Medium: Electronic Resource
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