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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 52 (1997), S. 383-386 
    ISSN: 1432-1041
    Keywords: Key words Ketotifen; pharmacokinetics ; children ; ␣clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Published pharmacokinetic data on ketotifen are sparse, although it is a commonly used prophylactic agent in various allergic disorders in adults and children. The aim of this study was to assess the steady-state pharmacokinetics of ketotifen in children with atopic perennial asthma who were participating in a clinical trial. Method: The NONMEM population approach with sparse sampling was utilized. The data set consisted of 239 samples from 48 children who were randomized to receive either 1 mg or 2 mg oral ketotifen daily. Patients underwent a clinical examination and had a blood sample taken at 2-week intervals for 12 weeks. The ketotifen concentrations were measured by RIA. Results: A one-compartment model with first-order absorption was fit to the data. Volume was estimated at 394 l and clearance (CL) at 97.4 l · h−1 (3.6 l · h−1 · kg−1). Weight or body surface area were the most influential covariates for explaining interindividual variability in CL. The 2-mg dose appeared to have a relative bioavailability of 85% of the 1-mg dose. Conclusion: Children have a faster clearance of ketotifen than adults and would therefore require a higher dose per kilogram body weight to give comparable steady-state levels.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 369-375 
    ISSN: 1432-1041
    Keywords: Theophylline ; children ; population pharmacokinetics ; Nonmem ; age ; gender ; race
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline clearance values in South African children were determined using 400 serum theophylline concentration measurements gathered from 109 compliant outpatients during their normal routine care. Population pharmacokinetic analysis was done using the Non-Linear Mixed Effects Model (Nonmem) to analyse the data. Nonmem was also used to estimate the influence of fixed effects (weight, age, race, gender etc) on clearance and its interindividual variability. Gender, age, and weight raised to an iterated exponent were found to be the most important demographic fixed effect parameters influencing clearance. Race was not found to be important. The weight-adjusted values of theophylline clearance decreased with increasing age. The actual values expressed in l·h−1·kg−1 were 0.0949 for children aged 1–5 y; 0.0813 for children aged 5–9 y, and 0.0660 for children of 9–16 y. The values are similar to those reported in other studies.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 48 (1995), S. 381-383 
    ISSN: 1432-1041
    Keywords: Phenobarbitone ; children ; population pharmacokinetics ; NONMEM ; concomitant medication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Non-linear Mixed Effects Modelling (NONMEM) was used to estimate phenobarbitone population clearance values for South African children, using 52 serum levels gathered from 32 patients during their routine care. NONMEM was also used to evaluate the influence of fixed effects such as weight, age and concomitant medication. The final model describing phenobarbitone clearance was CL=[Exp(0.0288 Wt−2.53)] M, where CL=clearance (l·h−1), Exp=the base of the natural logarithm, Wt=patient weight (kg) and M=a scaling factor for concomitant medication with a value of 1 for patients on phenobarbitone monotherapy, 0.62 for those receiving concomitant valproate and 0.87 for those patients receiving concomitant carbamazepine or phenytoin. Mean (95% confidence interval) phenobarbitone clearance values were 7.6 ml·h−1·kg−1 (6.2, 9.0 ml·h−1·kg−1) for the monotherapy group, 5.0 ml·h−1·kg−1 (4.0, 6.0 ml·h−1·kg−1) in the presence of concomitant valproate and 6.8 ml·h−1·kg−1 (5.6, 8.0 ml·h−1·kg−1) in the presence of concomitant carbamazepine or phenytoin. These values are similar to those previously reported from both traditional and NONMEM pharmacokinetic studies.
    Type of Medium: Electronic Resource
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