PubMed1984
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)