Ibuprofen in children with cystic fibrosis: Pharmacokinetics and adverse effects M i c h a e l W. Konstan, MD, Charles L. H o p p e l , MD, Bao-ling Chai, MD, a n d P a m e l a B. Davis, MD, PhD From the Departments of Pediatrics, Pharmacology, and Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio Antiinflammatory therapy with ibuprofen has been p r o p o s e d to retard the progression of lung disease in cystic fibrosis (CF). The pharmacokinetics a n d toxicity of ibuprofen were investigated in a randomized, double-blind, p l a c e b o controlled, 3-month dose-escalation study in 19 children with CF, 6 to 12 years of age. The subjects r e c e i v e d orally and twice daily 300 mg of drug during the first month, 400 mg in the s e c o n d month, and 600 mg in the third month. Ibuprofen pharmacokinetics a n d evaluation for adverse effects were performed at the beginning and end of e a c h month. The dose of ibuprofen was increased if p e a k plasma c o n c e n t r a t i o n (CmQx) was 3) giving an r value of >0.94 for the line. For the 49 studies the mean number of data points (_+ SD) used to define the terminal portion was 4.6 + 2.0 (range 3 to 8) and the r value was 0.992 + 0.009 (range 0.960 to 1.000). The line included the last detectable plasma concentration defined as ->0.5 gg/ml. The apparent terminal disposition rate constant

960

Konstan et al.

The Journal of Pediatrics June 1991

T a b l e II. Pharmacokinetics of ibuprofen from dose escalation in four children with CF

Mo I (300 mg) Dose (mg/kg)

10.0 38 68 5.8 1.8 85 211

Cmax (#g/ml)

Tmax(min) AUC (rag 9 min/rnl) C1/F (ml/min. kg -1) Tv2(min) Varea/F (ml/kg)

+ 2.3 _+ 3 --- 15 • 1.3 _+ 0.7 _+ 15 _+ 47

Mo 2 (400 mg) 13.2 29 128 6.3 2.1 93 282

• 3.2 • 9 • 38 • 0.9 • 0.4 _+ 6 • 69

Mo 3 (600 rng) 19.2 65 109 10.8 1.9 94 237

+ 4.7* _+ 14t _+ 97 _+ 3.1t • 0.6 • 38 • 70

Values expressed as mean + SD. *p