Pharmacokinetic and clinical studies with meropenem in the pediatric field

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summerized as follows. 1. Pharmacokinetic studies MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T 1/2's) of these doses were 28.5, 47.2 and 130.0μg/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T 1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 μg/ml at a dose of 6 mg/kg, and 0.64 to 4.22 μg/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalospolin antibiotics. 2. Clinical study Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave “exellent” or “good” responces in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave “exellent” or “good” responces in 77 cases (91.7%) and exellent bacteriological responces (95.7%). 3. Side effects and laboratory test results Among 403 cases, 6 symptoms were noted as side effects in 5 cases including diarrhea, rash, watery stools and loose stools. Abnormal laboratory results occurred in 58 cases including increases in GOT, GPT, 7-GTP, LDH, LAP and eosinophil counts, and decrease in neutrophil counts. Based on these results, we concluded that the standard dose of MEPM in pediatrics would be 10 to 20 mg/kg/once, 2 to 3 times a day. The dosage may be altered according to symptoms. In conclusion, MEPM is a useful and safe drug for the treatment of various infections in children including severe infectious diseases such as purulent meningitis and septicemia.