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  • 1
    Electronic Resource
    Electronic Resource
    Effect of meal timing on the kinetic-dynamic profile of levodopa/carbidopa controlled is release in parkinsonian patients (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 303-308 
    Details
    ISSN: 1432-1041
    Keywords: Key words Levodopa ; Controlled release formulations ; Parkinson's disease ; Meal interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of the study was to assess the effect of the time of ingestion of a meal on the pharmacokinetics and pharmacodynamics of a levodopa/carbidopa controlled-release formulation in parkinsonian patients on chronic levodopa therapy. Methods: The kinetic-dynamic profile of one tablet of controlled-release levodopa/carbidopa 200/50 mg was monitored in eight patients, according to an intrasubject randomized cross-over design in two different sessions. A standard meal was consumed by the patients after they had fasted for 15–17 h, on one occasion 30 min before the ingestion of the test dose, and on the other occasion 2 h after the ingestion of the same drug dose. Blood venous samples for analysis of plasma levodopa and its metabolite 3-O-methyldopa were drawn at 20-min intervals up to 6 h after dosing. Motor response to the levodopa test dose was assessed by the finger tapping and walking speed tests at the same times as blood was drawn. Results: Controlled is release levodopa intake after meals resulted in a significant delay in drug absorption, with an almost twofold increase in time of initial appearance of levodopa in plasma and time to peak plasma concentration. Peak plasma drug concentrations were not significantly different in the two experimental conditions; the area under the 6-h plasma concentration-time curve showed an average reduction of 24% in the fed condition, partly reflecting the incomplete assessment of levodopa absorption, within the 6 h of examination, due␣to 5-h delayed peak plasma levodopa concentration␣in two patients. With reference to levodopa pharmacodynamics, time to onset of motor response was significantly delayed and duration of motor response significantly curtailed in the fed condition, while the magnitude and overall extent of motor effect were unchanged. Conclusions: In keeping with previous findings on levodopa standard-release preparations, these data show that time of meal ingestion is an important determinant of levodopa disposition, even from controlled-release preparations in parkinsonian patients. From a clinical point of view, these results help to explain some of the delayed, curtailed and even lacking responses that often complicate afternoon motor performances in patients at the more advanced stages of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050464
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 463-466 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00626370
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  • 3
    Electronic Resource
    Electronic Resource
    Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian patients (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 59-67 
    Details
    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
    URL: http://dx.doi.org/10.1007/s002280050161
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