Renal handling of 2',3'-dideoxycytidine (ddC), a new anti-HIV dideoxyn
ucleoside which undergoes renal and non-renal clearance, was determine
d in CF-1 male mice. Since calmodulin inhibitors (CIs) and calcium cha
nnel blockers (CCBs) have been shown to influence the flux of pyrimidi
ne nucleosides across mammalian membranes and since the plasma concent
ration (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 secreti
on into renal tubules. Pre-exposure of mice to the calmodulin inhibito
rs loperamide (LOP) and trifluoperazine (TFP) resulted in a decrease i
n ddC renal secretion while pre-treatment with the calcium channel blo
cker verapamil increased ddC secretion.