British journal of clinical pharmacology
-
Br J Clin Pharmacol · Aug 2000
Randomized Controlled Trial Clinical TrialPharmacokinetics of epimeric budesonide and fluticasone propionate after repeat dose inhalation--intersubject variability in systemic absorption from the lung.
Pharmacokinetic variability is likely to be a significant factor contributing to the interindividual differences in dose requirements, anti-inflammatory response and side-effects with inhaled corticosteroids (ICS), but there is limited information about the disposition of ICS during regular dosing with a pressurized metered dose inhaler (pMDI). This study uses a mixed effects modelling approach to quantify and compare the interindividual variability in pharmacokinetics of epimeric budesonide (BUD) and fluticasone propionate (FP) after repeat-dose inhalation. ⋯ This is the first report describing the pharmacokinetics of epimeric BUD and FP after repeat dose inhalation via pMDI. Three observations may be of clinical relevance: (1) there is considerable intersubject variability in the rate of absorption of both drugs from the lung; (2) in some individuals there was a long t(1/2),z for BUD, resulting in higher and more sustained plasma drug levels in the 4-12 h postdose period than would be predicted from single-dose pharmacokinetic data; and (3) there is evidence of diurnal variation in FP pharmacokinetics, with higher-than-expected plasma drug concentrations in the morning compared with the evening.
-
Br J Clin Pharmacol · Aug 2000
A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children.
The aims of this study were to describe paracetamol pharmacokinetics in neonates and infants. ⋯ Total body clearance of paracetamol at birth is 62% and volume of distribution 174% that of older children. A target concentration above 10 mg l-1 in approximately 50% subjects can be achieved by a dose from 45 mg kg-1 day-1 at birth and up to 90 mg kg-1 day-1 in 5-year-old children. A reduced dose of 75 mg kg-1 day-1 in an 8-year-old child is sufficient because clearance is a nonlinear function of weight.