PHARMACOKINETIC AND CLINICAL STUDIES ON CEFMENOXIME IN NEONATES AND PREMATURE INFANTS

Abstract

Cefmenoxime (CMX) was administered by intravenous bolus injection to a total of 23neonates and premature babies with ages of 1 to 26 days at a dose of 10 or 20mg/kg and their plasma and urine concentrations and urinary recovery rates were determined up to 6 hours after administration. In addition, for the treatment of bacterial infections, diagnosed or suspected, or for the prophylaxis of bacterial infections, the drug was administered to a total of 27 neonates, premature babies and infants, with ages of 0 day to 3 months. It was possible to evaluate therapeutic efficacy and prophylactic efficacy in 15 cases and 7 cases, respectively. In these cases, side effects and bacteriological effects and, in some of them, changes in laboratory test values were also investigated. The obtained results are summarized below.
1. At a dosage level of 10mg/kg (n=7), peak plasma concentrations at 5 minutes after administration, were 42.6μg/ml in neonates with ages of 15 to 21 days and 45.9μg/ml in those with ages of 22 to 28 days in a group of <2,500g b. w.(birth weight), and 36.9μg/ml in neonates with ages of 4-7 days and 38.9μg/ml in those of 8-14 days in the other group of≥2,500g b. w., indicating no large differences among the 4 subgroups (each of the above concentration values is either the value for an individual when only one neonates was involved or a mean value when 2 or more neonates were involved. The same applies her inafter.). Though 1 exceptional case showed a biphasic change, its cause is unknown. Half-lives in the above-mentioned 4 subgroups were 1.5, 1.6, 2.4 and 1.9 hours, respectively. The half-life of 2.4 hours in 1 patient with an age of 5 days of the ≥2,500g b. w. group was longer than in any of the other 3 subgroups.
2. At 20mg/kg (n=16) dosage level, mean peak plasma concentrations were 63.8μg/mlin the infants of 0-3 days, 68.1 μg/ml in those of 8-14 days and 59.4μg/ml in those of 15-21 days in the group of<2,500g b. w., and 109.9μg/ml in the neonates aged 8-14 daysand 79.7μg/ml in those of 15-21 days in the group ≥2,500g b.w. The mean concentration in the 0-3 days old subgroup of the<2,500g b. w. group was the highest at 15 minutes after administration, partly because the peak concentration in one 3-day-old neonate in this group occurred at 15 minutes after administration rather than 5 minutes after administration though thecause of this delay is unknown. Some variations such as the above were observed in individual values or in mean values. Three cases showed biphasic changes due to unknown caused. The mean half-life was longest at 4.0 hours in the 0-3 days old subgroup (<2,500g b. w.) because, in this subgroup, one neonate with age of 1 day showed a remarkably prolonged half-life of 6.0 hours. The mean half-lives in the other 4 subgroups were 1.9, 1.4, 1.5 and 1.9 hours, respectively.
3. In 7 cases given CMX at 10mg/kg, it was possible to determine urine concentrations of the drug in all or some of the periods during 0-2, 2-4 and 4-6 hours after administration and the values were in a range of 9.86 to 1,245.0μg/ml. The 0-6 hour urinary recovery rates were 56.7% in the neonates of ages ranging 15-21 days and 64.6% in those of ages ranging 22-28 days in the group of <2,500g b. w., and 36.7% in the neonates of 4-7 days and 73.5% in those of 8-14 days in the group of≥2,500g b. w. The rate in the 4-7 day subgroup (≥2,500g b. w.), though the subgroup consisted of 1 case only, was lower than in any of the other 3 subgroups.
4. In 16 cases given the drug at 20mg/kg, it was possible to determine urine concentrations in all or some of the periods during 0-2, 2-4 and 4-6 hours after administration and the values were in a range of 70.1 to 3,330.0μg/ml.