1986 Volume 39 Issue 7 Pages 1847-1865
Pharmacokinetic and clinical studies on imipenem (MK-0787)/cilastatin sodium (MK-0791), a combined drug of carbapenem antibiotics (MK-0787) and renal depeptidase inhibitor (MK-0791) in a 1: 1 ratio, were performed in the field of pediatrics.
1. Absorption and excretion
Serum levels and urinary excretion of MK-0787/MK-0791 were determined in 7 children aged 4 to 11 years. Four cases were administered with a single dose of MK-0787/MK-0791 at 10mg/10mg/kg by intravenous drip infusion and the other 3 cases were given a single dose of 20mg/20mg/kg.
Serum concentrations of MK-0787 reached their peaks at the end of drip infusion where the mean level was 17.5±1.0μg/ml for the group given 10mg/10mg/kg, and 43.6±2.1μg/ml for the group given 20mg/20mg/kg. Concentrations decreased with half-lives of 0.82±0.10 hour and 0.74±0.04 hour for the low and high doses, respectively, and serum levels at 6 hours after administration were 0.3±0.1μg/ml and 0.4±0.1μg/ml, respectively. Peak concentrations of MK-0791 were 22.6±4.8μg/ml in the 10mg/10mg/kg group and 52.9±4.7μg/ml in the 20mg/20mg/kg group at the end of the drip infusion. Half-lives were 0.56±0.17 hour and 0.46±0.11 hour for the 2 doses, respectively while MK-0791 levels were below detection limit at 6 hours after administration.
Mean urinary recovery rates in 6 hours after administration were 54.0±15.3% and 49.3±7.8% for MK-0787 and MK-0791, respectively, in the group of 10mg/10mg/kg, and 62.0±7.4% and 65.3±9.2%, respectively, in the group of 20mg/20mg/kg. These results showed that pharmacokinetics of MK-0787 and MK-0791 in children were similar to that in adults.
2. Clinical study
MK-0787/MK-0791 was used for treatment in a total of 22 pediatric patients to evaluate clinical effectiveness, bacteriological efficacy and adverse reactions. Each of patients was treated 3 or 4 times per day at a single dose of 11.4-22.8mg/kg (of MK-0787). Duration of treatment ranged from 2.5 to 18 days and total doses ranged from 1.36 to 19.92g.
Clinical efficacy in cases including 2 with acute purulent tonsillitis, 1 with acute purulent otitis media, 9 with acute pneumonia, 1 with pythorax, 3 with acute purulent lymphadenitis, and 6 with acute pyelonephritis were judged excellent in 20 cases and good in 2 cases; an efficacy rate of 100%.
Causative organisms isolated from these patients included 4 strains of E. coli, 3 strains of H. influenzae, and 1 strain each of S. aureus, S. pneumoniae, H. parainfluenzae, K. pneumoniae and P. aeruginosa. All the organisms were eliminated by the treatment, thus the bacteriological eradication rate was 100%.
No adverse reactions were observed. Among clinical laboratory findings, there was 1 case with elevated Bilirubin, GOT and GPT, another case with elevated GOT and GPT, 2 cases with only elevated GOT, and 3 cases with increased platelet. But these abnormalities were transient, and returned to normal after discontinuation of the drug in all the cases except one (elevation of only GOT) which was not tested any further.
From the above results, it has been concluded that MK-0787/MK-0791 is a very useful and safe drug for use in the field of pediatrics.
