Pharmacokinetics of penicillin G in infants with a gestational age of less than 32 weeks.
The pharmacokinetics of penicillin G were studied in 20 preterm neonates with a gestational age of less than 32 weeks on day 3 of life by using a population approach performed with the nonlinear mixed effects modeling program NONMEM. The derived population estimates and the correlation matrix of these estimates were used to perform Monte Carlo simulations and obtain the probability of target attainment (PTA). The pharmacokinetics of penicillin G were best described by a two-compartment pharmacokinetic model. The population estimates of the central volume of distribution, the peripheral volume of distribution, the intercompartmental clearance, and the total body clearance were 0.359 +/- 0.06 liter, 0.152 +/- 0.03 liter, 0.774 +/- 0.28 liter/h, and 0.103 +/- 0.01 liter/h (mean +/- standard error), respectively. The terminal half-life was 3.9 h. Clearance increased significantly with increasing birth weight. Assuming the percentage of time that the concentration of unbound drug remained above the MIC of 50% for preterm neonates, the susceptibility breakpoint based on a 100% PTA was < or =4 mg/liter, simulating the current dosing regimen of 50,000 U/kg every 12 h. This regimen is therefore adequate for the treatment of common infections in neonates on the third day of life.
Muller
Anouk E
AE
Medical Centre Haaglanden (MCH), Department of Obstetrics and Gynecology, Lijnbaan 32, 2512 VA, The Hague, The Netherlands. a.muller@mchaaglanden.nl
DeJongh
Joost
J
Bult
Ymka
Y
Goessens
Wil H F
WH
Mouton
Johan W
JW
Danhof
Meindert
M
van den Anker
John N
JN
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005865:Gestational Age; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D010400:Penicillin G / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011153:Population; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism; D012727:Sex Characteristics; D013269:Stochastic Processes
D000900:Anti-Bacterial Agents; D010400:Penicillin G