Calmodulin inhibitors and calcium channel blockers influence dideoxycytidine renal excretion.

Renal handling of 2',3'-dideoxycytidine (ddC), a new anti-HIV dideoxynucleoside which undergoes renal and non-renal clearance, was determined in CF-1 male mice. Since calmodulin inhibitors (CIs) and calcium channel blockers (CCBs) have been shown to influence the flux of pyrimidine nucleosides across mammalian membranes and since the plasma concentration (and hence the efficacy) of therapeutic nucleosides is usually affected by the rate of renal elimination, we decided to determine the impact of the CIs loperamide (LOP) and trifluoperazine (TFP) as well as the CCB verapamil (VER) on the renal excretion of ddC. The ratio of ddC clearance to inulin clearance suggests that ddC undergoes secretion into renal tubules. Pre-exposure of mice to the calmodulin inhibitors loperamide (LOP) and trifluoperazine (TFP) resulted in a decrease in ddC renal secretion while pre-treatment with the calcium channel blocker verapamil increased ddC secretion.