PHARMACOKINETICS OF INTRAVENOUSLY AND INTRAMUSCULARLY ADMINISTERED CEFEPIME IN INFANTS AND CHILDREN

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) w ith a group of 37 infants and children, In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intraveno us dose, and disposition characteristics were studied again, Study sub jects ranged in age from 2.1 months to 16.4 years, and all had normal renal function, Each patient received 50 mg of cefepime/kg of body wei ght intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cef epime dose for surgical prophylaxis, the patients received cefepime fo r 2 to 13 days. Elimination half-life (t(1/2)), steady-state volume of distribution, total body clearance, and renal clearance after first d ose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/m in/kg, respectively. Although cefepime t(1/2) and mean residence time (MRT) were slightly longer for subjects <6 months of age than for olde r subjects, no differences in cefepime disposition characteristics bet ween first dose and steady-state evaluations were observed. t(1/2) (1. 8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged aft er intramuscular administration, reflecting the influence of absorptio n from the intramuscular injection site on cefepime elimination. Bioav ailability after intramuscular administration averaged 82% (range, 61 to 124%), Fifty-seven percent of the first dose and 88.9% of the last dose were recovered as unchanged drug in urine over the 8- and 24-h sa mpling periods, respectively. These pharmacokinetic data support a sin gle cefepime dosing strategy for patients greater than or equal to 2 m onths of age. The integration of the cefepime pharmacokinetic data gen erated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients greater than or equal to 2 months of age to treat infections caused by pathogens for which cefepime MICs are less than or equal to 8 mg/liter.