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Pharmacokinetics of Ibuprofen in Patients with Cystic Fibrosis
Author(s) -
Murry Daryl J.,
Oermann Christopher M.,
Ou ChingNan,
Rognerud Cheryl,
Seilheimer Dan K.,
Sockrider Marianna M.
Publication year - 1999
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.19.4.340.30944
Subject(s) - ibuprofen , pharmacokinetics , volume of distribution , medicine , cystic fibrosis , body surface area , body weight , pharmacology
Study Objectives. 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. Design. 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. Setting. Medical school‐affiliated teaching hospital. Patients. Ninety‐eight patients with CF (53 males, 45 females; mean age 12.5 yrs). Measurements and Main Results. The time to achieve apparent maximum ibuprofen concentration (T max ) ranged from 1–3 hours, with maximum concentrations ranging from 21–150 μg/ml (mean 83 μg/ml). Apparent ibuprofen clearance (Cl/F) was significantly correlated with age (r 2 = 0.43, p<0.0001) and measures of body size (body surface area [BSA] r 2 = 0.50, p<0.0001). The Cl/F ranged from 21.1–114.7 ml/min/m 2 (mean 45.5 ml/min/m 2 ), 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 (r 2 = 0.69, p<0.0001) and measures of body size (BSA r 2 = 0.79, p<0.0001). Fourteen patients had ibuprofen dosage adjustments. The Cl/F was not different among doses; however, T max differed by an average of 1.25 hours (range 0–2 hrs). Conclusion . 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.