[A clinical phase I study on intramuscular imipenem/cilastatin sodium]

The safety and pharmacokinetics of imipenem/cilastatin sodium (IPM/CS) were evaluated in comparative studies using single intramuscular injection, intravenous infusion or multiple intramuscular administration. The studies were done employing 30 healthy volunteers. Adverse effects were observed in 5 of 18 volunteers in the single intramuscular dose study. One of them complained of mild itching and mild pain at the injection site, and the other 4 volunteers had mild pain at the injection sites. With the other methods of administration, no adverse effects were observed. No other abnormal physical findings nor abnormal laboratory test values were observed in any of the studies. Imipenem (IPM) was absorbed rather slowly through the muscles, resulting in a low maximum plasma concentration (Cmax) and a prolonged half life (T1/2) upon intramuscular injection compared to the results obtained upon intravenous infusion. The total areas under the curves obtained with these 2 methods were similar, however. Cilastatin (CS) was absorbed rapidly after intramuscular injection, and the Cmax obtained was higher than that obtained for IPM. The T1/2 and the AUC of CS obtained with intramuscular injection were similar to those obtained with intravenous infusion. Cumulative urinary recovery rates obtained with these 2 different routes of administration were not different. Detectable urinary levels of IPM were maintained much longer upon intramuscular injection than upon intravenous infusion. In the multiple dose study, neither IPM nor CS showed tendency to accumulate.