Abstract
Imipenem/cilastatin sodium (IPM/CS) was administered in a dose of 10mg/10mg/kg or 20mg/20mg/kg by a 1-hour intravenous drip infusion to 19 mature and premature neonates with ages from 1 to 12 days with various bacterial infections, and plasma concentrations and urinary recovery rates in these subjects were measured. Because of the small number of patients recruited, neonates were not divided into mature and premature groups, but into 3 groups based on their day-ages: 0-3 days, 4-7 days and 8 days or older.
A clinical evaluation of IPM/CS was carried out in 10 male and 3 female neonates with ages 0-28 days. These patients included 6 with pneumonia, 4 with urinary tract infection and 1 each with septicemia, suspected septicemia and maxillary sinusitis.
1. Plasma concentrations and urinary recovery rates
(1) The 1-hour intravenous drip infusion at 10mg/10mg/kg of IPM/CS
IPM: Its peak plasma concentrations were obtained at the end of drip infusion of the test drug in all 3 groups, their values ranged from 18.18 to 19.90μg/ml with no statistically significant variations. The plasma concentrations rapidly decreased to 0.32-0.98μg/ml at 8 hours after administration of IPM/CS. The half-lives tended to be shorter in older neonates, with mean half-lives being 1.87, 1.55 and 1.40 hours, respectively.
CS: Its peak plasma concentrations were obtained for all 3 groups at the end of drip infusion and were ranging from 28.23 to 30.00μg/ml with no significant variations. Plasma concentrations in the 0-3 day-age group and the4-7 day-age group slowly decreased to 6.30μg/ml and 4.58μg/ml at 8 hours after administration of IPM/CS, respectively. Half-lives were 4.10 hours and 3.08 hours, respectively. On the other hand, those of the 8-day or older group rapidly decreased to below the detection limit in 8 hours after administration with a half-life of 1.6 hours.
(2) The 1-hour intravenous drip infusion at 20 mg/20mg/kg of IPM/CS
IPM: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 31.1 to 38.24 μg/ml. Plasma concentrations rapidly decreased, and were 0.95-2.08μg/ml at 8 hours after administration with half-lives of 1.5-1.88 hours.
CS: Peak plasma concentrations were obtained in all 3 groups at the end of drip infusion and were ranging from 47.0 to 55.82μg/ml. Plasma concentrations at 8 hours after administration were higher in younger neonates, i. e., 14.75μg/ml in the 0-3 day-age group, 9.40μg/ml in the 4-7 day-age group and 4.0μg/ml in the 8-day or older group. Differences in half-lives in different age groups were large, i. e., 4.48 hours in the 0-3 day-age group, 3.30 hours in the 4-7 day-age group and 2.1 hours in the 8-day or older group.
(3) Urinary recovery
The urinary recovery of IPM and CS in 8 hours after administration ranged from 21.6 to 57.3% and from 47.5 to 96.0%, respectively. In the IPM/CS 10mg/10mg/kg group, the urinary excretion rates of CS tended to increase in the older neonates.
2. Clinical results
Thirteen patients with various bacterial infections were treated with IPM/CS from 24.7/24.7 to 65.2/65.2mg/kg/day b. i. d. or t. i. d. by intravenous drip infusion.
The clinical efficacy was either excellent or good in all patients. Causative organisms were isolated from 12 out of 13 patients (Staphylococcus aureus from 4 patients, Escherichia coli from 4, Klebsiella pneumoniae from 2, group B Streptococcus from 1 and Haemophilus influenzae+Enterobacter cloacae from 1). All organisms were eradicated after IPM/CS treatment.
No adverse reaction was observed. Abnormal laboratory test values were noted in 1 patient with elevated GOT and GPT.
