title: [Pharmacokinetics and clinical efficacy of imipenem/cilastatin sodium in neonates].
abstract: Clinical pharmacology and clinical efficacy and safety of imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic with a carbapenem nucleus and a dehydropeptidase-I inhibitor, were investigated in newborns. 1. Peak serum concentrations of IPM/CS at a dose of 20 mg/20 mg/kg were achieved at the end of 60-minute infusion. Maximum serum levels of IPM and CS were 44.2 micrograms/ml and 70.0 micrograms/ml, respectively, in neonates with ages 0-3 days. IPM and CS peak levels in premature infants with ages 0-3 days were 47.2 micrograms/ml and 56.1 micrograms/ml, respectively. IPM and CS peak levels in neonates 4 day-old or older were 35.0 micrograms/ml and 41.5 micrograms/ml, respectively, and in premature infants of similar ages were 45.7 micrograms/ml and 65.3 micrograms/ml, respectively. 2. Mean serum half-lives of IPM and CS in 0-3 day-old neonates were 1.6 hours and 3.1 hours, respectively, and the mean serum half-lives in premature infants were 2.1 hours and 4.6 hours, respectively. In neonates 4 day-old or older, the mean serum half-lives of IPM and CS were 1.6 hours and 2.6 hours, respectively, and in premature infants they were 1.5 hours and 1.9 hours, respectively. 3. A dose response was evident between doses of 10 mg/10 mg/kg and 20 mg/20 mg/kg of IPM and CS. 4. Urinary recovery rates of IPM for the 0- to 6-hour post IPM/CS infusion period ranged between 27.2 and 46.6%. For CS, urinary recovery rates for the 0- to 6-hour post IPM/CS infusion period ranged between 25.3 and 100.8%. 5. Clinical efficacy was evaluated in 9 patients and 7 patients showed excellent or good responses. 6. Of 14 patients who received IPM/CS treatment, 1 patient showed hematuria, leukopenia and thrombocytopenia, and 3 patients showed eosinophilia. However, these adverse reactions improved after the completion of therapy. 7. IPM has excellent antimicrobial activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria. In this study, coadministration of IPM and CS produced good clinical responses and no serious adverse reactions. It is hence concluded that IPM/CS sodium is very useful for the treatment of severe bacterial infections in neonates, especially in the presence of beta-lactamase resistant strains and in polymicrobial infections.
authors.affiliation: Department of Pediatrics, School of Medicine, Keio University.
authors.forename: S
authors.initials: S
authors.lastname: Azagami
authors.forename: Y
authors.initials: Y
authors.lastname: Kusumoto
authors.forename: T
authors.initials: T
authors.lastname: Oikawa
authors.forename: M
authors.initials: M
authors.lastname: Osano
authors.forename: H
authors.initials: H
authors.lastname: Shiro
authors.forename: Y
authors.initials: Y
authors.lastname: Shirai
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000042:Absorption; D000367:Age Factors; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D001724:Birth Weight; D015377:Cilastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004341:Drug Evaluation; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male
chemical_list: D015377:Cilastatin; D015378:Imipenem