[Pharmacokinetic and clinical studies on imipenem/cilastatin sodium in neonates and premature infants].
Imipenem/cilastatin sodium (IPM/CS) was administered in a dose of 10 mg/10 mg/kg or 20 mg/20 mg/kg by a 1-hour intravenous drip infusion to 19 mature and premature neonates with ages from 1 to 12 days with various bacterial infections, and plasma concentrations and urinary recovery rates in these subjects were measured. Because of the small number of patients recruited, neonates were not divided into mature and premature groups, but into 3 groups based on their day-ages: 0-3 days, 4-7 days and 8 days or older. A clinical evaluation of IPM/CS was carried out in 10 male and 3 female neonates with ages 0-28 days. These patients included 6 with pneumonia, 4 with urinary tract infection and 1 each with septicemia, suspected septicemia and maxillary sinusitis. 1. Plasma concentrations and urinary recovery rates (1) The 1-hour intravenous drip infusion at 10 mg/10 mg/kg of IPM/CS IPM: Its peak plasma concentrations were obtained at the end of drip infusion of the test drug in all 3 groups, their values ranged from 18.18 to 19.90 micrograms/ml with no statistically significant variations. The plasma concentrations rapidly decreased to 0.32-0.98 microgram/ml at 8 hours after administration of IPM/CS. The half-lives tended to be shorter in older neonates, with mean half-lives being 1.87, 1.55 and 1.40 hours, respectively. CS: Its peak plasma concentrations were obtained for all 3 groups at the end of drip infusion and were ranging from 28.23 to 30.00 micrograms/ml with no significant variations. Plasma concentrations in the 0-3 day-age group and the 4-7 day-age group slowly decreased to 6.30 micrograms/ml and 4.58 micrograms/ml at 8 hours after administration of IPM/CS, respectively. Half-lives were 4.10 hours and 3.08 hours, respectively. On the other hand, those of the 8-day or older group rapidly decreased to below the detection limit in 8 hours after administration with a half-life of 1.6 hours. (2) The 1-hour intravenous drip infusion at 20 mg/20 mg/kg of IPM/CS IPM: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 31.1 to 38.24 micrograms/ml. Plasma concentrations rapidly decreased, and were 0.95-2.08 micrograms/ml at 8 hours after administration with half-lives of 1.5-1.88 hours. CS: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 47.0 to 55.82 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
Toyonaga
Y
Y
Department of Pediatrics, Jikei University, School of Medicine.
Sugita
M
M
Hori
M
M
Joh
K
K
D000367:Age Factors; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; 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; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male
D015377:Cilastatin; D015378:Imipenem