Pharmacokinetics of penicillin g in very-low-birth-weight neonates

Abstract

Data on the pharmacokinetics (PKs) of penicillin G (PEN) in neonates date back to the 1970s and do not include data for very-low-birth-weight (VLBW) neonates. The aim of this study was to describe the steady-state PKs and to establish an optimal regimen for the dosing of PEN in neonates with gestational ages of less than 28 weeks and birth weights of less than 1,200 g. Two PEN dosing regimens were studied: 50,000 IU (30 mg)/kg of body weight every 12 h (q12h) (group 1; n = 9) and 25,000 IU (15 mg)/kg q12h (group 2; n = 9). Samples for PK analysis were drawn before the injection of PEN and at 2 and 30 min and 1.5, 4, 8, and 12 h after intravenous injection of the third to eighth PEN doses. The PEN concentration was measured by a high-performance liquid chromatography with UV detection technique. The median peak and trough concentrations of PEN were 147 mug/ml (lower and upper quartiles, 109 and 157 mug/ml, respectively) and 7 mug/ml (lower and upper quartiles, 5 and 13 mug/ml, respectively) after administration of the dose of 50,000 IU and 59 mug/ml (lower and upper quartiles, 53 and 78 mug/ml, respectively) and 3 mug/ml (lower and upper quartiles, 3 and 4 mug/ml, respectively) after administration of the dose of 25,000 IU. The PEN half-life (median and lower and upper quartiles for group 1, 3.9 h and 3.3 and 7.0 h, respectively; median and lower and upper quartiles for group 2, 4.6 h and 3.8 and 5.6 h, respectively) was longer in VLBW neonates than in adults and term infants. PEN renal clearance correlated with creatinine clearance (R(2) = 0.309596; P = 0.038). Only a median of 34% (lower and upper quartiles, 28 and 37%, respectively) of the administered dose was excreted in urine within the following 12 h. We conclude that in VLBW infants a PEN dose of 25,000 IU (15 mg)/kg q12h is safe and sufficient to achieve serum concentrations above the MIC(90) for group B streptococci for the entire dosing interval.

FIG. 1.

Individual time-concentration curves of intravenous PEN in VLBW infants receiving PEN doses of 50,000 IU/kg (left) and 25,000 IU/kg (right). Dotted line, the patient accidentally received PEN at a dose of 83,300 IU (50 mg)/kg; the data for this patient were excluded from calculations of the PK parameter values for group 1; bold line, an infant born at the 26th week of gestation with a BW of 700 g had clinical edema and a PEN t_1/2 of 35.1 h; the data for this patient were included in the calculations of the PK parameter values for group 1.

FIG. 2.

Correlation between PEN and creatinine CL_R: PEN CL_R (ml/min) = 0.221987 CL_CR (ml/min) + 0.233152 (R² = 0.309596; P = 0.038).