PHARMACOKINETIC AND CLINICAL STUDIES OF CEFOTIAM IN NEONATES AND PREMATURE INFANTS

Abstract

Cefotiam (CTM) was given to 25 mature and premature infants, ranging in age from 0 to 24 days, who have various nearly-healed bacterial infections. CTM was administered at the dose of 10mg/kg by intravenous injections or by 1-hour intravenous drip infusions, or at the dose of 20mg/kg by intravenous injections. Only a small number of subjects being examined, they were divided by their aged day into 3 groups; 0-3 days old, 4-7 days old and 8-24 days old. We compared the time courses of changes in serum and urine levels of CTM in these groups.
The clinical study was done with 8 male and 4 female infants ranging in age from 3 days to 4 months. One had septicemia, 4 had bronchopneumonia, 3 had urinary tract infection, 1 had colitis, 2 had abscess, and 1 had maxillary sinusitis.
1. Changes in serum and urinary levels of CTM
(1) Changes in serum levels after 10mg/kg intravenous injection.
Peak serum CTM levels of all 3 groups were achieved at 30 minutes after administration; the levels were between 11.7 and 23.6μg/ml; and differences were not significant. Serum levels then gradually decreased in all the groups to 0.5-7.0μg/ml at 6 hours after administration. Half-lives of serum CTM levels tended to be shorter in older infants; means were 2.7, 2.2 and 1.3 hours for the 0-3 day-old, the 4-7 day-old and the 8-24 day-old respectively.
(2) Changes in serum levels of CTM after 10mg/kg 1-hour intravenous drip infusion.
The 0-3 day-old and the 4-7 day-old had peak serum CTM levels, ranging from 16.3 to 35.8μg/ml, at the end of drip infusion. Half-lives of serum CTM levels tended to be shorter in older infants, with 3.2 hours for the 0-3 day-old and 2.0 hours for the 4-7 day-old groups.
(3) Changes in serum levels after 20mg/kg intravenous injection.
The 0-3 day-old and the 4-7 day-old had peak serum levels, ranging from 30.6 to 42.1μg/ml, at 30 minutes after administration, then serum levels of CTM in either group showed a gradual decrease to 2.5-11.4μg/ml at 6 hours after injection.
(4) Changes in urinary levels of CTM after intravenous injection and 1-hour intravenous drip infusion.
Proportions of CTM excreted in the 0-6 urine after administration of 10mg/kg CTM were 33.6-58.2% by intravenous injection and 22.3-34.0% by 1-hour intravenous drip infusion, respectively. On 1 patient given by intravenous injection of 20mg/kg, urinary excretion rate of 46.2% was observed in 8 hours after the injection.
2. Clinical results
The CTM was used in a total of 12 patients. The CTM was given by intravenous injection to 11 of the 12 patients (administration was by 30 minute intravenous drip infusion for the other patient), two or three times a day at doses of 42.1 to 133.9mg/kg/day for 3 to 13 days. Results were either good or excellent in all 12 cases; the efficacy rate was 100%. Causative bacteria were eradicated in 11 of the 12 patients (E. coli in 4 patients, S. aureus in 4, K. pneumoniae in 1, S. epidermidis in 1 and K. pneumoniae+S. aureus in 1). In the other case, bacteriological result was not clear.
The drug produced no adverse symptoms or side effects in any of the 12 patients, except an increase in GOT observed in 1 patient.