FUNDAMENTAL AND CLINICAL STUDIES OF CEFSULODIN IN THE NEONATES AND PREMATURE INFANTS

Abstract

Fourteen neonates and premature infants with ages ranging 1 to 28 days were intravenously given one shot injection of 20mg/kg of cefsulodin (CFS). Plasma and urine levels and recovery rates of CFS were determined in the first 6 hours after administration. For prophylaxis of infection, a daily average dose of 52.8mg/kg of CFS was injected intravenously to 3 neonates with ages ranging 2 to 16 days in 2 to 3 divided doses during an average period of 7 days. Along with observations of prophylactic effects on infection, side effects and abnormalities in laboratory test values were examined. The results obtained are summarized below:
1. Of the 9 patients with birth weight of 2,500g or above, the plasma levels peaked in 6 patients at 5 minutes, in 2 patients at 15 minutes and in the other at 1 hour after administration, with peak levels ranging between 35.8 and 60.6μg/ml. Subsequently, gradual decreases or bimodal tapering changes were noted in the plasma levels. The cause of the delay in the occurrence of maximum peak observed in the 3 patients at 15 minutes or 1 hour after administration and the cause of the appearance of bimodal tapering changes in 3 subjects are not known. A tendency was observed that the younger the age of subject was, the larger the AUC and the longer the half-life became. Half-lives in all 9 neonates were longer than those in average infants who were given intravenous injection at the same dose.
2. Of 5 patients with birth weight of less than 2,500g, the determination of peak plasma levels was not performed in those within 7 days after birth. Plasma levels, however, were observed to reach their peaks in 4 patients at 5 minutes and in another at 15 minutes after administration, the levels ranging between 41.5 and 56.0μg/ml. Subsequently to this, gradual decreases and bimodal tapering changes of plasma levels were noted. The cause of the delay in plasma levels to reach their maximum peaks values in the 1 patient to 15 minutes after administration and the cause of occurrence of bimodal tapering changes in the 2 partients are not known. A tendency was observed that the younger the age of subjects was, the larger the AUC and the longer the half-life became. This tendency was similar to that observed in the group with birth weight of 2,500g or above. Half-lives in all 5 neonates were longer than those in average infants who were given intravenous injection at the same dose.
3. Urine levels of the drug were measurable in 9 patients with birth weight of 2,500g or above in during 0 to 2, 2 to 4, and 4 to 6 hours after administration, and they ranged between 120.0 and 1,890.0μg/ml. In 5 patients with birth weight of less than 2,500g, urinary levels were measurable during the above specified periods of time, and the measured levels ranged between 65.1 and 619.0μg/ml.
4. In the group with birth weight 2,500g or above, the mean or individual urine recovery rates in the first 6 hours after administration in patients with their ages 3 or less, 4 to 7, 8 to 14, 15 to 21, and 22 to 28 days were 29.7, 46.2, 45.6, 49.2, and 55.5%, respectively. There was only one patient in the 3 or less day-age group and the urine recovery rate of this subject was lower than those of the other age groups. In the group with birth weight of less than 2,500g, urine recovery rate of the drug was not determined in any of them in the first 7 day after birth. However, mean or individual urine recovery rates in the first 6 hours after administration in patients with ages 8 to 14, 15 to 21, and 22 to 28 days were 40.7, 48.9 and 29.9%, respectively. Those in the 22 to 28 day-age group exhibited lower urine recovery rates than those of the other 2 age groups, but the cause for the low recovery rates is unknown.