Review of the pharmacokinetics of cefepime in children

Background. Because determining the pharmacokinetics of drugs used in pediatric patients allows for appropriate dosing and optimal clinical response, we have reviewed the pharmacokinetic data on the use of cefepime in the pediatric population. Methods, Three studies encompassing 88 patients ages 2 months to 16 years examined the pharmacokinetics of cefepime given as a single iv dose, as multiple iv doses and by im administration, In all studies serial blood and urine or cerebrospinal fluid (CSF) samples were collected after a single dose and/or at steady state, defined as after at least 2 days of dosing. Pharmacokinetic parameters were generated from concentration-vs.-time curves and were analyzed using noncompartmental methods. Results. In all studies cefepime exhibited a linear pharmacokinetic profile and concentrations declined proportionally over time. Minimal accumulation was observed after multiple dosing. Pharmacokinetic parameters were similar in all studies and appeared to be dose-independent. Mean (range) parameters observed in this review were: t(1/2) = 1.7 h (1.26 to 1.93); volume of distribution at steady state, 0.37 liter/kg (0.33 to 0.40); total body clearance, 3.1 ml/min/kg (1.43 to 4.01); renal total body clearance, 2.3 ml/min/kg (1.86 to 3.05); absolute bioavailability of cefepime after the im dose, 82.3%; and urinary recovery, 72% (57 to 85%). Penetration into CSF appeared to be good, with CSF concentrations averaging 3.3 to 5.7 mug/ml 0.5 and 8 h after administration of the dose, respectively. Conclusion, Cefepime displayed a linear pharmacokinetic profile, was well-absorbed via im injection and had adequate penetration into the CSF of patients with bacterial meningitis, compared with other beta-lactams.