Pharmacokinetics of ibuprofen in patients with cystic fibrosis.
OBJECTIVE
To determine the pharmacokinetic disposition of high doses of ibuprofen in patients with cystic fibrosis (CF), and to evaluate the reliability of intrapatient dosage adjustments to achieve recommended peak ibuprofen plasma concentrations.


METHODS
First-order absorption, one-compartment model was fit to serial ibuprofen concentration-time data obtained from patients with CF and receiving high doses of ibuprofen 20-30 mg/kg.


METHODS
Medical school-affiliated teaching hospital.


METHODS
Ninety-eight patients with CF (53 males, 45 females; mean age 12.5 yrs).


RESULTS
The time to achieve apparent maximum ibuprofen concentration (Tmax) ranged from 1-3 hours, with maximum concentrations ranging from 21-150 microg/ml (mean 83 microg/ml). Apparent ibuprofen clearance (Cl/F) was significantly correlated with age (r2 = 0.43, p<0.0001) and measures of body size (body surface area [BSA] r2 = 0.50, p<0.0001). The Cl/F ranged from 21.1-114.7 ml/min/m2 (mean 45.5 ml/min/m2), a 5-fold difference. The Cl/F normalized to body weight decreased with increasing age (p=0.0009), but when normalized to BSA, there was no age-related change (p=0.65). Apparent volume of distribution was significantly correlated with age (r2 = 0.69, p<0.0001) and measures of body size (BSA r2 = 0.79, p<0.0001). Fourteen patients had ibuprofen dosage adjustments. The Cl/F was not different among doses; however, Tmax differed by an average of 1.25 hours (range 0-2 hrs).


CONCLUSIONS
The substantial variability in ibuprofen disposition and clearance we report is greater than previously described. Individualized dosages and therapeutic drug monitoring may be required to ensure plasma concentrations considered necessary to prevent pulmonary deterioration in patients with CF.
Murry
D J
DJ
Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, USA.
Oermann
C M
CM
Ou
C N
CN
Rognerud
C
C
Seilheimer
D K
DK
Sockrider
M M
MM
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016013:Likelihood Functions; D008297:Male; D012044:Regression Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen