Review of the pharmacokinetics of cefepime in children

Background. Because determining the pharmacokinetics of drugs used in pedia tric patients allows for appropriate dosing and optimal clinical response, we have reviewed the pharmacokinetic data on the use of cefepime in the ped iatric population. Methods, Three studies encompassing 88 patients ages 2 months to 16 years e xamined the pharmacokinetics of cefepime given as a single iv dose, as mult iple iv doses and by im administration, In all studies serial blood and uri ne 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. Pharmac okinetic parameters were generated from concentration-vs.-time curves and w ere 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 simila r in all studies and appeared to be dose-independent. Mean (range) paramete rs observed in this review were: t(1/2) = 1.7 h (1.26 to 1.93); volume of d istribution at steady state, 0.37 liter/kg (0.33 to 0.40); total body clear ance, 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-a bsorbed via im injection and had adequate penetration into the CSF of patie nts with bacterial meningitis, compared with other beta-lactams.