Related Experiment Videos
Cimetidine enhances cisplatin toxicity in mice
1Department of Internal Medicine, College of Medicine and Pharmacy, University of Arizona, Tucson.
Journal of Cancer Research and Clinical Oncology
|January 1, 1988
Summary
The histamine H2 antagonist cimetidine (CMT) can increase the toxicity of the anticancer drug cisplatin (CDDP) in mice. This combination altered CDDP toxicity without impacting its effectiveness against tumors.
Area of Science:
- Pharmacology
- Oncology
- Toxicology
Background:
- Cimetidine (CMT), a histamine H2 antagonist, is often used to manage acid reflux.
- Cisplatin (CDDP) is a widely used platinum-based chemotherapy agent for various cancers.
Purpose of the Study:
- To investigate the combined effects of cimetidine (CMT) and cisplatin (CDDP) in preclinical models.
- To determine if CMT influences the toxicity and/or efficacy of CDDP.
Main Methods:
- Experiments were conducted using tumor-bearing and normal mice.
- Mice received varying doses of CDDP alone or in combination with CMT.
- Survival rates and lethality were monitored and analyzed using Wilcoxon analysis.
Main Results:
- In DBA/2J mice with P388 leukemia, CMT (100 mg/kg) did not alter survival when combined with low CDDP doses (3-6 mg/kg).
- In CD-1 mice, higher CDDP doses (10-18 mg/kg) combined with CMT significantly increased CDDP-induced lethality.
- CMT-enhanced lethality ranged from 10% to 100% depending on the CDDP dose administered.
Conclusions:
- Cimetidine can acutely modify the toxicity profile of cisplatin in mice.
- The observed increase in CDDP lethality by CMT occurred independently of changes in antitumor efficacy.