Cladribine inhibits a diltiazem-induced increase in red blood cell purine nucleotide concentrations in a zebrafish model.
Minimizing drug interactions is paramount to improving the efficacy and tolerability of cancer therapy. The zebrafish represents an innovative cancer model due to highly conserved genetics and inherent capacity for high-throughput chemical screening. This pilot study extends the utility of the zebrafish to a preclinical model for pharmacodynamics by examining the interaction of the nucleoside analogue, cladribine with the calcium channel blocker, diltiazem. Cladribine (0.7-3.5 mM) and/or diltiazem (2.4 mM), was injected intraperitoneally into adult zebrafish and red blood cell (RBC) lysates were assayed by HPLC for levels of purine nucleotides (e.g. ATP), potential biomarkers of cardiovascular health. Diltiazem increased RBC ATP concentrations, which were inhibited by co-injection of cladribine. These results suggest a novel drug interaction and highlight the feasibility of the zebrafish as an in vivo model for pharmacodynamic studies.
Klein
Lauren C
LC
IWK Health Centre, Dalhousie University, Nova Scotia, Canada.
Yeung
Pollen K
PK
Berman
Jason N
JN
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D017338:Cladribine / Q000627:therapeutic use*; D004110:Diltiazem / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects*; D023421:Models, Animal; D010865:Pilot Projects; D011685:Purine Nucleotides / Q000097:blood*; D015027:Zebrafish
D015415:Biomarkers; D011685:Purine Nucleotides; D017338:Cladribine; D000255:Adenosine Triphosphate; D004110:Diltiazem