Pharmacokinetics of ibuprofen enantiomers in children with cystic fibrosis.
Chiral inversion of R(-)- to S(+)-ibuprofen in children with cystic fibrosis was investigated. Children with cystic fibrosis (n = 38, ages 2-13 years) were administered a single oral dose of racemic ibuprofen (20 mg/kg), and the pharmacokinetics of ibuprofen was found to be stereoselective. Mean Cmax, AUC, apparent CL/F, and Varea/F of S-ibuprofen were significantly different from those of R-ibuprofen. The enantiomeric ratio of plasma AUC (S:R = 2.09:1) and of free and conjugated ibuprofen in urine (S:R = 13.9:1) of children with cystic fibrosis was not different from reported values for healthy children and adults. No significant gender difference was observed for any of the pharmacokinetic parameters determined. However, there was an inverse linear relationship between the CL/F of R-ibuprofen and age in children with cystic fibrosis. Apparent CL/F was higher in children with cystic fibrosis than previously reported for healthy children; therefore, higher doses of ibuprofen would be necessary for children with cystic fibrosis.
Division of Drug Delivery and Disposition, School of Pharmacy, School of Medicine, University of North Carolina at Chapel Hill 27599-7360, USA.
J Q
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Dong
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C S
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Scott
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Retsch-Bogart
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Smith
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000493:pharmacokinetics*; D008297:Male; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen