Abstract
IMP/CIL is a new combination β-lactam antibiotic which possesses potent in vitro activity against a broad range of pathogens commonly isolated from premature (P) and newborn infants. To assess dosing requirements, P were assigned to 10, 15, 20 or 25 mg/kg IMP/CIL intravenously over 15 to 40 min either as single or multiple doses. 30 P (670-1890 gm) from 24.5-36 weeks gestation were studied. All were studied during the first dose (FD); 12 were restudied after at least 10 doses (SS) given q12h. All studies were performed during the first week of life. Multiple blood and urine samples (over 8-12 hrs) were obtained for the determination of IMP/CIL by HPLC. Pharmacokinetic (PK) analysis was performed using standard non-compartmental methods. Total (n=29) FD PK revealed mean (±SD) IMP: 11/2=2.4(0.3), Vdss=0.5(0.1)L/kg, CI=47(12) ml/min/1.73m2 and CIL: t1/2=8(2.8), Vdss=0.4(0.1)L/kg, and CI=10.5(3.5) ml/min/1.73m2. IMP/CIL renal CI averaged 8.7(4.2) and 4.0(2.5) ml/min/1.73m2, respectively. No differences were observed in PK parameters (except AUC) for the different doses studied or between IMP FD and SS evaluations. In contrast, SS CIL AUC and t1/2 were decreased and body CI increased from FD (p<0.02). IMP/CIL AUC correlated directly with dose administered: FD IMP r=0.74 and CIL r=0.64. Peak IMP/CIL concentrations averaged 23.6 and 32.1 mg/L after 10 mg/kg FD increasing linearly over the dose range studied. A direct relationship between post conceptual age (PCA) and FD IMP/CIL body CI(r=0.61/0.55) and renal CI (r=0.31/0.68) was observed. No drug related toxicities were observed in any P. Depending on PCA, doses should range from 15 to 25 mg/kg administered q12h to maintain therapeutic peak and trough IMP serum concentrations. CIL body CI increases rapidly and to a greater extent than IMP during the first week of life.
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Reed, M., Kliepman, R., Yamashita, T. et al. THE CLINICAL PHARMACOLOGY OF IMIPENEM (IMP) AND CILISTATIN (CIL) IN PREMATURE INFANTS. Pediatr Res 21 (Suppl 4), 241 (1987). https://doi.org/10.1203/00006450-198704010-00441
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DOI: https://doi.org/10.1203/00006450-198704010-00441