Abstract
Fundamental and clinical studies were carried out on imipenem/cilastatin sodium (MK-0787/MK-0791) in pediatric patients. The following results were obtained.
1. A total of 238 clinical isolates stocked by our department was employed to determine the minimum inhibitory concentrations (MICs) of MK-0787 against various species of bacteria. The MK-0787 showed strong antibacterial activities against E. coli, Salmonella, Klebsiella, Proteus, Serratia, E. faecalis and S. epidermidis. Somewhat weaker activities were observed against P. aeruginosa and S. aureus.
2. The MK-0787/MK-0791 was drip-infused intravenously into patients over a period of 1 hour, and serum levels of MK-0787 and MK-0791 were determined. At the dose level of 10mg/10mg/kg, the mean serum levels of MK-0787 and MK-0791 were 29.9μg/ml and 18.1μg/ml at 1 hour and 3.4μg/ml and 1.3μg/ml at 3 hours, respectively. The half-lives were 0.89 hour for MK-0787 and 0.99 hour for MK-0791.
At the dose level of 20 mg/20mg/kg, the mean serum levels of MK-0787 and MK-0791 were 46.3μg/ml and 45.2μg/ml at 1 hour and 5.5μg/ml and 3.1μg/ml at 3 hours, respectively. The half-lives were 0.97 hour for MK-0787 and 0.83 hour for MK-0791.
At the dose level of 40mg/40mg/kg, the mean serum levels of MK-0787 and MK-0791 were 104.0μg/ml and 80.9μg/ml at 1 hour and 7.8μg/ml and 5.9μg/ml at 3 hours, respectively. The half-lives were 0.92 hour for MK-0787 and 0.53 hour for MK-0791.
3. The total urinary recovery was determined for the first 6 hours after administration of MK-0787/MK-0791. The recovery was 9.5-105.9% for MK-0787 and 4.6-113.0% for MK-0791.
4. The penetration of MK-0787 and MK-0791 into the cerebrospinal fluid ranged from 3.0-8.3% of serum levels for MK-0787 and 1.1-10.8% for MK-0791.
5. The MK-0787/MK-0791 was administered to 13 patients with bacterial infections. Good or excellent clinical effects were observed in 12 patients (92.3%).
6. Eradication of bacteria was observed in all of 8 patients who were evaluated bacteriologically.
7. As a side effect, diarrhea was observed in 1 patient. Abnormalities in laboratory findings observed were thrombocytosis in 2 patients, elevation of GOT and direct bilirubin in 1, and elevation of GOT and GPT in 1 patient.
