FUNDAMENTAL AND CLINICAL STUDIES OF LATAMOXEF IN THE NEONATES AND IMMATURE INFANTS

Abstract

Latamoxef (LMOX) was administered as a one-shot intravenous injection of 10mg/kg or 20mg/kg to 28 newborn and immature infants of 1 to 28 days of age.For 6 hours following the administration, the concentrations of the drug in the plasma and in the urine were monitored and the urinary recovery rate was determined.
In addition, 17 patients, consisting of newborns, immature infants and suckling infants, aged 0 days to 2 months and diagnosed as having various bacterial infections, were also treated with LMOX;the mean daily dosage was 103mg/kg, administered in 2 to 6 divided doses as one-shot intravenous injections for an average duration of 11 days.These patients were subjected to the analysis for the clinical efficacy and bacteriological efficacy of the therapy.Furthermore, with the inclusion of 35 drop-out cases, a total of 52 patients was investigated for the occurrence of side effects by the LMOX therapy.The findings of these studies are summarized below.
1. The patients were divided into 5 groups on the basis of age: 3 days old or less, 4-7 days, 8-14 days, 15-21 days and 22-28 days.Only in the 8-14 day-old group administered LMOX at 20mg/kg, the maximum mean plasma concentration of the drug occurred at the time of 15 minutes postadministratin, although some individuals showed peaks at 5 minutes.In all of the other age groups, for both the 10 and 20 mg/kg dosings, the maximum plasma concentration of LMOX occurred 5 minutes postinjection.In each of the age groups, a dose response was seen between the 2 dosage levels.However, a comparison of each group and control infants in terms of the LMOX plasma concentration at 30 minutes after injection revealed that the concentrations in the patients in this study were low.In terms of the half-life of the drug at the 2 dosage levels, both the mean and individual values in each of the age groups were longer than the half-lives in control infants.This tendency was especially marked in the case of infants 7 days of age or less.The values for the AUC also tended to be larger in the younger patient groups.
2. A good level of LMOX was detected in the urine during each of the 0-2, 2-4 and 4-6 hour periods following administration.When considering those patients for whom it was possible to determine the urinary concentration at each time, it was found that the maximum LMOX concentration occurred in the 0-2 hour period or the 2-4 hour period, in each of the age groups and regardless of the LMOX dosage level.The mean and individual values for the 6 hour urinary recovery rate were low in each of the age groups compared with the control infants, again regardless of the LMOX dosage level.However, there was a tendency for the recovery rate to increase in parallel with the age of the patient.
3. The clinical efficacy rate of the LMOX therapy was 64.7% in the 17 patients diagnosed as having various bacterial infections.With regard to the bacteriological effect of the LMOX, the causative microorganism was eradicated in 5 out of 6 of the patients, while no change occurred in the sixth patient.
4. A total of 52 patients was analyzed for side effects; these consisted of the 17 patients who were evaluated for the clinical efficacy of LMOX, plus 35 patients who were drop-outs from that clinical study.No cases of side effects were found to have developed in any of these patients.As abnormal laboratory test values, there were 4 cases (incidence: 10.3%) of eosinophilia, and 1 case of mild elevation of BUN.Otherwise, when consideration is given to the use of concomitant drugs and hemolysis of the test serum, it can be concluded that there were no other cases of laboratory test value abnormalities.