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- Title
The effect of different doses of cisplatin on the pharmacokinetic parameters of cefepime in mice.
- Authors
András Máthé; Kinga Komka; Mónika Forczig; Dóra Szabó; Piroska Anderlik; Ferenc Rozgonyi
- Abstract
The simulation of human serum levels is essential in animal models to extrapolate the experimental results to clinical practice. Administration of a nephrotoxic drug such as cisplatin can be used to cause renal dysfunction as an approach to mimic human serum levels of renally excreted drugs. We aimed to determine the dose of cisplatin that did not affect the survival rate of mice and to achieve human-like serum concentrations of cefepime. Different doses of cisplatin (0, 10, 14, 18, 22 and 26 mg/kg) were given by intraperitoneal (i.p.) injection to mice three days prior to the i.p. administration of 80 mg/kg cefepime. With cisplatin doses of 18 and 22 mg/kg, the half-life of cefepime was significantly prolonged (P<0.001) and all mice survived. The pretreatment with 26 mg/kg cisplatin significantly decreased survival (P=0.001), but the half-life of cefepime was not significantly longer than of 18 mg/kg cisplatin. Serum levels of cefepime after the pretreatment with 18 mg/kg cisplatin were comparable to published human data. The administration of cisplatin appears to be a suitable method in mice for simulating human serum concentrations of renally excreted drugs.
- Subjects
COORDINATION compounds; ALKYLATING agents; ANTINEOPLASTIC agents; METAL-ammonia compounds
- Publication
Laboratory Animals, 2006, Vol 40, Issue 3, p296
- ISSN
0023-6772
- Publication type
Article