Pharmacokinetics of penicillin G in infants with a gestational age of less than 32 weeks
Abstract number: 1733_867
Muller A.E., DeJongh J., Bult Y., Goessens W.H., Mouton J.W., Danhof M., van den Anker J.N.
Objectives: Infectious complications in the immediate postnatal period are common and especially premature infants are vulnerable. Penicillin G is often given in such cases, but the pharmacokinetics in premature infants may differ substantially and is largely unknown, in particular in infants with a gestational age of less than 32 weeks. We investigated the pharmacokinetics of penicillin G in this age group.
Methods: Infants with a gestational age of less than 32 weeks on day 3 of life were eligible for the study. They received 50.000 EH/kg penicillin G every 12 h intravenously. From each patient 69 blood samples were taken. Antibiotic concentrations were determined by a validated HPLC method. Pharmacokinetic parameters were estimated by population pharmacokinetic modeling using NONMEM. Various models were tested. To discriminate between models the minimum value of objective function (MVOF) was used.
Results: Twenty intants were included. A two-compartment pharmacokinetic model best described the time course of penicillin G. Clearance (CL), volume of the central compartment (Vc) and intercompartimental clearance were estimated at respectively 0.103±0.01 L/h, 0.359±0.06 L and 0.774±0.277 L/h (mean±SE). The residual error was found to be both proportional and additive to the blood concentrations. Interindividual variability was found for CL and Vc. The volume of distribution at steady state was 0.54L and terminal half-life was 3.9 h. CL increased significantly with body weight. The relationship between gestational age and CL was examined, but found to be inferior to the relationship between body weight and CL.
Conclusions: The pharmacokinetics of penicillin in infants with a gestational age of less than 32 weeks differs significantly from that in adults and children with a prolonged mean terminal half-life of approximately 4 hours. These results warrant a dosing schedule of two times daily dosing in this age group. CL significantly increased with body weight, rather than with gestational age.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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