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  • 1
    Electronic Resource
    Electronic Resource
    Alpha1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine-10,11 epoxide in children with epilepsy (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 211-214 
    Details
    ISSN: 1432-1041
    Keywords: carbamazepine ; epilepsy ; carbamazepine-10,11 epoxide ; alpha1-acid glycoprotein ; serum protein binding ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the serum protein binding of carbamazepine (CBZ) and carbamazepine-10,11 epoxide (CBZ-E) and the concentration of α1-acid glycoprotein (AAG) and albumin (HSA) was examined in 39 CBZ-treated epileptic children aged 4 months to 12 years. A significant inverse correlation was found between the free fraction of both compounds and serum AAG, even though changes in AAG concentration explained only part of the variation in binding. No correlation was found between the free fraction of CBZ and CBZ-E and HSA, probably due to the small intersubject variation in HSA concentration. In vitro experiments showed that both CBZ and CBZ-E were bound to HSA and to a lesser extent to AAG. At equivalent HSA concentrations, the binding of CBZ and its metabolite increased proportionately with increasing AAG concentration within the range occurring clinically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547424
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  • 2
    Electronic Resource
    Electronic Resource
    Altered serum protein binding of carbamazepine in disease states associated with an increasedα 1-acid glycoprotein concentration (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 85-89 
    Details
    ISSN: 1432-1041
    Keywords: carbamazepine ; serum protein binding ; alpha1-acid glycoprotein ; albumin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of carbamazepine (CBZ) in vitro was assessed in sera from 47 patients with various diseases known to alterα 1-acid glycoprotein (AAG) concentration and from 20 drug-free normal control subjects. In the patient group, AAG and albumin (HSA) concentrations ranged from 6 to 74 µmol/l and from 377 to 652 µmol/l, respectively; in the controls, protein concentrations were less variable, ranging from 11 to 26 µmol/l for AAG and from 623 to 754 µmol/l for HSA. In both the patient and the combined patient and control groups, free CBZ fractions were inversely correlated with the serum AAG concentration (r=−0.62). No significant relationship could be found between the free CBZ fraction and the serum HSA concentration. The free CBZ fraction was moderately but significantly decreased in patients with AAG levels above 26 µmol/l (the highest value found in controls) as compared either to patients with a normal AAG concentration or to control subjects (19±5% vs 23±4% and 23±2%), despite the finding of a higher HSA concentration in the control group. The data confirm AAG as an important determinant of interindividual variability in serum CBZ binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00870992
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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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