Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Pharmacokinetics of Diltiazem and its Major Metabolite, Deacetyldiltiazem after Oral Administration of Diltiazem in Mild and Medium Folate-Induced Renal Failure Rabbits

  • Published : 2001.08.01
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Abstract

The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg was given to the rabbits either orally (n=6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration ($C_{max}$) of DTZ were significantly increased in mild and medium folate-induced renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly decreased in mild and medium folate-induced renal failure rabbits. The volume of distribution ($V_{d}$) and total body clearance ($CL_{t}$) of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimination rate constant ($\beta$) of DTZ was significantly decreased in folate-induced renal failure rabbits, but that of DAD was significantly increased. These findings suggest that the hepatic metabolism of DTZ was inhibited and the $V_{d}$, $CL_{t}$ and $\beta$ of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.

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References

  1. Biopharm. Drug Dispos. v.12 Bioavailabiltity of diltiazem as a function of the administered dose Bianchetti,G.;Regazzi,M.;Rondanelli,R.;Ascalone,V.;Morselli,P.L.
  2. J. Cardiovasc. Pharmacol. v.6 Clinical pharmacology of calcium antagonists Eichelbaum,M.;Echizen,H.I.
  3. Am. J. Kidney Dis. v.16 Effects of calcium antagonists on renal hemodynamics Epstein,M.;Loutzenhiser,R.D.
  4. Am. J. Kidney Dis. v.345 High performance liquid chromatographic dertermination of diltiazem and four of its metabolites in plasma Goebel,K.J.;Kolle,E.U.
  5. J. Clin. Pharmacol. v.28 Pharmacokinetics of diltiazem in patients undergoing continuous ambulatory peritoneal dialysis Grech-Belanger,O.;Langlois,S.;LeBoeuf,E.
  6. Eur. J. Clin. Pharmacol. v.24 Pharmcokinetics of diltiazem after intravenous and oral administration Hermann,P.;Rodger,S.D.;Remones,G.;Thenot,J.P.;London,D.R.
  7. Pharm. Res. v.12 Metabolism of diltiazem in hepatic and extrahepatic tissues of rabbits Homsy,W.;Lefebvre,M.;Caille,G.;du Souich P.I.
  8. Drug Metab. Dispos. v.15 Deacetylation of diltiazem by rat liver Leboeuf,F.;Grech Belanger,O.I.
  9. Pharm. Res. v.12 Decreased systemic clearance of diltiazem with increased hepatic metabolism in rats with uranyl nitrate-induced acute renal failure Lee,Y.H.;Lee,M.H.;Shim,C.K.
  10. J. Pharmco. l Exp. Ther. v.279 Enhanced inhibition of microsomal cytochrome P-450 in rat liver during diltiazem biotransformation Murray,M.;Butler,A.M.
  11. Eur. J. Pharmacol. v.24 Pharmacokinetics of diltiazem in severe renal failure Pozet,N.;Brazier,J.L.;Aissa,A.H.;Khenfer,D.;Faucon,G.;Apoil,E.;Traeger,J.
  12. Cardiovasc. Drugs Ther. v.4 Renal effects of calcium entry blockers Ruilope,L.M.;Alcazar,J.M.
  13. Chem. Pharm. Bull. v.19 The whole body autoradiographic studies on the disposition of 14C-labeled new 1,5-benzothiazepine derivative(14C-CRD-401)in mice Sakuma,M.;Yoshikawa,M.;Sato,Y.
  14. Cardiovasc. Drugs Ther. v.10 Pharmacological aspects of calcium channel blockers Scholz,H.
  15. J. Cardiovasc. Pharmacol. v.10 Renal actions of calcium antagonists Sterzel,P.B.
  16. J. Pharmacol. Exp.Ther. v.282 Role of CYP3A4 in human hepatic diltiazem N-deme-thylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolite Sutton,D.;Butler,A.M.;Nadin,L.;Murray,M.I.
  17. Biopharm. Drug Dispos. v.12 Pharmacokinetics of intravenous diltiazem and five of its metabolites in patients with chronic renal failure and in healthy volunteers Tawashi,M.;Marc Aurele,J.;Bichet,D.;Spenard,J.;Lariviere,L.;Plante,D.;Caille,G.E.
  18. Biopharm. Drug. Dispos. v.12 Pharmacokinetics of oral diltiazem and five of its metabolites in patients with chronic renal failure Tawashi,M.;Marc Aurele,J.;Bichet,D.;Spenard,J.;Lariviere,L.;Plante,D.;Caille,G.E.
  19. J. Pharm. Dyn. v.4 A pharmacokinetics analysis program for microcomputer Yamaoka,K.;Tanigawara,Y.;Nakagawa,T.;Uno,T.