       Document 0689
 DOCN  M9650689
 TI    Calmodulin inhibitors and calcium channel blockers influence
       dideoxycytidine renal excretion.
 DT    9605
 AU    Enigbokan MA; West D; Preston J; Thompson JO; College of Pharmacy and
       Health Sciences, Texas Southern; University, Houston 77004, USA.
 SO    Cell Mol Biol (Noisy-le-grand). 1995;41 Suppl 1:S15-8. Unique Identifier
       : AIDSLINE MED/96171630
 AB    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.
 DE    Animal  Ca(2+)-Transporting ATPase/PHYSIOLOGY  Calcium/PHYSIOLOGY
       Calcium Channel Blockers/*PHARMACOLOGY  Calmodulin/*ANTAGONISTS & INHIB
       Kidney Tubules/*DRUG EFFECTS/METABOLISM  Loperamide/PHARMACOLOGY  Male
       Metabolic Clearance Rate/DRUG EFFECTS  Mice  Support, U.S. Gov't, P.H.S.
       Trifluoperazine/PHARMACOLOGY  Verapamil/PHARMACOLOGY
       Zalcitabine/BLOOD/*PHARMACOKINETICS/URINE  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

