Pharmacokinetics of ticarcillin during cisplatin chemotherapy

Cancer chemotherapeutic agents and antimicrobial antibiotics are often given concomitantly. Cisplatin, which has become increasingly important in cancer treatment, has shown nephrotoxicity as a dose-limiting feature. The alpha-carboxy-penicillin ticarcillin (tc) has a wide spectrum of antimicrobial activity, especially against Pseudomonas. The plasma half-life of tc is correlated with renal function. The combined use of cisplatin (20 mg/m2, days 1-5) and tc (3 X 5 g/24 h, days 1-5) with renal protection by vigorous hydration (2400 ml of 0.9% NaCl/24 h continuous infusion, days 1-5) in a group of 12 cancer patients did not alter the BUN and creatinine serum levels. The mean serum concentration of tc, which was monitored in a patient 15, 30, and 45 min after injection of 5 g on 4 consecutive days together with cisplatin, did not differ from the levels of tc reported when used without concomitant cisplatin therapy. Thus these preliminary data show that the pharmacology of tc may not be altered significantly when applied together with cisplatin and that cumulative nephrotoxicity must not be expected with this combination when sufficient hydration is used.