[A pharmacokinetic investigation of sisomicin administered intramuscularly to children].
For the purpose of studying the pharmacokinetic profile of sisomicin (SISO) and the proper conditions for its administration to children, SISO was administered intramuscularly to 10 infants aged less than 1 year, 16 young children and 18 school children at doses of 1.0, 1.5 and 2.0 mg/kg and its serum and urine levels were determined by bioassay. The mean peak levels of SISO in serum appeared at 1/4 hour in the infants, irrespective of the dose; the mean peak levels were 2.27, 3.05 and 4.83 micrograms/ml after the 1.0, 1.5 and 2.0 mg/kg doses, respectively. In the young children, the mean peak levels appeared at 1/4 hour after the 1.0 mg/kg dose and at 1/2 hour after both the 1.5 mg/kg and 2.0 mg/kg doses. The mean peak levels were 2.82, 3.80 and 6.43 micrograms/ml, respectively. In the school children, the mean peak levels appeared at 1/2 hour after all the doses and were 4.34, 5.31 and 6.87 micrograms/ml, respectively. The mean peak levels were in the order of school children greater than young children greater than infants and were dose-dependent. In the infants, the mean urinary recovery was 43.7% for the 1.0 mg/kg dose and 31.2% for the 1.5 mg/kg dose; in the young children, 50.5, 35.9 and 65.6% for the 1.0, 1.5 and 2.0 mg/kg doses, respectively; and in the school children, 54.2, 50.2 and 56.7%. Using the observed serum levels, the pharmacokinetic parameters were calculated according to the one-compartment open model theory. (1) The mean elimination rate constants (K) were calculated at 0.60, 0.67 and 0.56 hr-1 for the infants, young children and school children, respectively. There were found no great differences among the above 3 age groups. The mean absorption rate constants (ka) were 18.5, 7.6 and 5.9 hr-1 and the apparent volumes of distribution per kg body weight, Vd (L/kg), 0.44, 0.26 and 0.22 L/kg, respectively. These 2 parameters were significantly greater in the infants than in the young children and school children. The maximum serum concentration (Cmax) and the time when the concentration reaches a maximum (Tmax) were substantially in agreement with the observed values. The half-lives (T1/2) were 1.16, 1.03 and 1.23 hours for infants, young children and school children, respectively, and did not differ significantly among the 3 groups. A serum level simulation curve constructed by plotting the mean values for K, ka and Vd did not reveal any substantial deviation from the observed values.(ABSTRACT TRUNCATED AT 400 WORDS)
D000293:Adolescent; D000367:Age Factors; D001419:Bacteria / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D007700:Kinetics; D008954:Models, Biological; D012853:Sisomicin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
D012853:Sisomicin