Pharmacokinetics of intravenously and intramuscularly administered cefepime in infants and children

Abstract

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects 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 weight 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 cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6 months of age than for older subjects, no differences in cefepime disposition characteristics between first dose and steady-state evaluations were observed. t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after intramuscular administration, reflecting the influence of absorption from the intramuscular injection site on cefepime elimination. Bioavailability 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 sampling periods, respectively. These pharmacokinetic data support a single cefepime dosing strategy for patients > or =2 months of age. The integration of the cefepime pharmacokinetic data generated 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 > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.

Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review

“…The pharmacokinetic parameters by Lima-Rogel et al [64] and those by Capparelli et al [52] were obtained in infants with similar demographic data t 1/2 and Cl are comparable in these two studies. Reed et al [63] described the pharmacokinetics of cefepime in older infants and children and in this study, t 1/2 was one half and Cl was double those in the neonates. Cl ranged from 1.1 and 2.7 mL/min/mg, Vd ranged between 0.41 and 0.43 L/kg and t 1/2 ranged from 1.9 to 4.9 h. …”

“…Gestational age and postnatal age have an important effect on Cl and consequently on t 1/2 of penicillins [10,14,15,18,20,22,23,29], cephalosporins [33,38,42,43,45,57,60,63] and aminoglycosides [78,79,85,86,107]. Thus, gestational and postnatal ages are factors generating interindividual variability in the pharmacokinetics of penicillins, cephalosporins and aminoglycosides.…”

“…Lima-Rogel et al [64] compared their own results on the pharmacokinetics of cefepime in neonates with those by Capparelli et al [62] and with those by Reed et al [63]. The pharmacokinetic parameters by Lima-Rogel et al [64] and those by Capparelli et al [52] were obtained in infants with similar demographic data t 1/2 and Cl are comparable in these two studies.…”

“…Reed et al [63] described the pharmacokinetics of cefepime in 37 infants and children aged between 2 months and 16 years. The data are grouped on age; the youngest patients ranged between 2 and 6 months of age and the pharmacokinetic results of these patients are reported in Table 4.…”

Pharmacokinetics of cephalosporins in the neonate: a review

“…Reed et al39 described the pharmacokinetics of cefepime in 37 infants and children aged between 2 months and 16 years. The data were grouped by age; the youngest patients ranged between two and six months of age, and the pharmacokinetic parameters of cefepime in these patients are reported in Table 3.…”