ABSTRACT
During in vitro experiments using pooled human plasma at 37 degrees C, sisomicin alone showed only a small loss of activity of 12% in 24 hr. Incubation with 80 micrograms/ml mezlocillin did not alter the rate of inactivation. But, after the addition of 300 micrograms/ml mezlocillin to either 5.0 or 2.5 micrograms/ml sisomicin, the sisomicin half-life was reduced by 50% and 100% respectively. When the mean drug concentration ratios are compared, inactivation of sisomicin by mezlocillin was significantly less than that reported for carbenicillin or ticarcillin. Sisomicin pharmacokinetics were studied in 27 patients with normal and various degrees of impaired renal function (Part A) and were not changed by the simultaneous administration of mezlocillin 60 mg/kg (Part B). Furthermore, even in far advanced renal insufficiency, sisomicin inactivation by mezlocillin could not be demonstrated. The differing results obtained with mezlocillin compared to carbenicillin or ticarcillin might be explained by differences in the physico-chemical properties of the drugs in addition to the different kinetic behavior of mezlocillin in patients with impaired renal function.
