Archives of Pharmacal Research

  • 제17권6호
  • /
  • Pages.428-433
  • /
  • 1994
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Metabolism and Pharmacokinetics of S-(N,N-Diethyldithiocar-bamoyul)-N-acetyl-L-cysteine in Rats

  • Lee, Byung-Hoon (Doping Control Center, Korea Institute of Science and Technology) ;
  • Song, Yun-Seon (Doping Control Center, Korea Institute of Science and Technology) ;
  • Park, Jongsei (Doping Control Center, Korea Institute of Science and Technology) ;
  • Ryu, Jae-Chun (Doping Control Center, Korea Institute of Science and Technology)
  • 발행 : 1994.12.01
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초록

The methabolism and phamacokinetics of a mixed disulfide S-(N, N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) were studied in rats. Two metabolites of AC-DDTC following iv and po administration were indentified in plasma and liver by HPLC and GC, namely N, N-diethyldithiocarbamate (DDTC) and the methyl ester of DDTC (Me-DDTC). AC-DDTC was very unstable in vivo and could not be detected neither in plasma nor in urine. Pharmacokinetic parameters of DDTC following intravenous administration of AC-DDTC (20 mg/kg) were calculated. DDTC has a low affinity to rat tissue and the body clearance was $9.0{\pm}3.4mkl/mim/kg$. The mean residence time (MRT) was $11.5{\pm}16.3 min$. After oral administration of 20 mg/kg AC-DDTC, maximal plasma concenttion ($C_{max}$) was $3.8{\pm}0.2 nmol/ml$ and the bioavailability was 7.04%. $C_{max}$ for DDTC at a dose of 120 mg/kg. AC-DDTC was $40.1{\pm}2.2 nmol/ml$. ART was $47.1{\pm}2.8min$.at a dose of 20 mg/kg and $110.5{\pm}6.0 min$ at 120 mg/kg.

키워드

참고문헌

  1. Ann. Rev. Pharmacol. Toxicol. v.21 The action and metabolic fate of disulfiram Eneanya,D.I.;Bianchine,J.R.;Duran,D.O.;Andersen,B.D.
  2. Alcohol Clin. Exp. Res. v.2 Distribution of radioactivity in rats after ip and oral $S_{35}$ disulfiram(DSF) administration Faiman,M.D.;Haya,K.;Artman,L.
  3. Biochem. Pharmacol. v.21 Diethyldithiocarbamic acid methyl ester. A metabolite of disulfiram Gessner,T.;Jakubowski,M.
  4. Pharmacokinetics Gibaldi,M.;Perrier,D.
  5. Alcohol v.7 S-Methyl-N,N-diethylthiocarbamate : A disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibior Hart,B.W.;Yourick,J.J.;Faiman,M.D.
  6. Chem Pharm. Bull. v.29 Urinary metabolites of 1-(3-mercapto-2-D-methyl-1-oxopropyl)-L-proline (SQ-14225), a new antihypertensive agents in rats and dogs Ikeda,T.;Komai.T.;Kawai,K.;Shindo,H.
  7. Biochem. Biophys. Acta v.71 Formation of an S-glucuronide from tetraethylthiuramdisulfide (Antabuse) in man Kaslander,J.
  8. J. Med. Chem. v.37 Sugar-linked dithiocarbamates as modulators of metabolic and genotoxic properties of N-nitroso-compounds Lee,B.H.;Bertram,B.;Schmezer,P.;Frank,N.;Wiessler,M.
  9. Arzneim.-Forsch./Drug Res. v.37 Inhibitory effects of mixed disulfides from disulfiram on the metabolism and genotoxicity of N-nitrosodiethylamine Lee,B.H.;Bertram,B.;Rajca,A.;Frank,N.;Schmezer,P.;Wiessler,M.
  10. Drug Metab. Dispos. The fate and idstribution of [¹⁴C]S-(N,N-diethyl-dithiocarbamoyl)-N-acetyl-L-cysteine in rats Lee,B.H.;Ryu,J.C.;Park,J.;Bertram,B.;Wiessler,M.
  11. Toxicol. Appl. Pharmacol. v.97 Determination and metabolism of dithiol chelating agents;Ⅵ. Isolation and identification of the mixed disulfides of meso-2,3-dimercaptosuccinic acid with L-cysteine in human urine Maiorino,R.M.;Bruce,D.C.;Aposhian,H.V.
  12. J. Natl Cancer Inst. v.64 Inhibitory effect of disulfiram on rat mammary tumor induction by N-2-fluorenylacetamide and on its metabolic conversion to N-hydroxy-N-2-fluorenylacetamide Malejka-Giganti,D.;Mclver,R.C.;Rydell,R.E.
  13. J. Chromatogr. v.224 Simultaneous determination of disulfiram and two of its dithiocarbamate metabolites in human plasma by reversed-phase liquid chromatography Masso,P.D.;Kramer,P.A.
  14. Arzneim.-Forsch./Drug Res. v.40 New mixed disulfides of L-cysteine derivatives and of glutathione with diethyldithiocarbamic acid and 2-mercaptoethane sulfonic acid Rajca,A.;Bertram,B.;Eisenbarth,J.;Wiessler,M.
  15. J. Cancer Res. Clin Oncol. v.116 no.suppl. Stability and cell transport of mixed disulfides from disulfiram plus acetylcysteine or glutathione Rajca,A.;Eisenbarth,J.;Lee,B.H.;Bertram,B.;Wiessler,M.
  16. J. Biol. Chem. v.238 Metabolism of thiopyrimidines and thiopurines. S-Methylation with S-adenosylmethionine transmethylase and catabolism in mammalian tissues Remy,C.
  17. J. Appl. Toxicol. v.12 The effects of probenecid on the excretion kinetics of stanozolol, an anabolic steroid, in rats Ryu,J.C.;Kwon,O.S.;Song,Y.S.;Yang,J.S.;Park,J.
  18. Biochem. J. v.242 Inactivation of horse liver mitochondrial aldehyde dehydrogenase by disulfiram: Evidence that disulfiram is not an active-site-directed reagent Sany,C.G.;Weiner,H.
  19. PKCALC Shumaker,R.C.
  20. BioChem. Pharmacol. v.12 Effects of diethyldithiocarbamate and disulfiram on glucose metabolism and glutathione content of human erythrocytes Stomme,J.H.
  21. Biochem. Pharmacol. v.14 Interaction of disulfiram and diethyldithiocarbamate with serum proteins studied by means of gel-filtration technique Stromme,J.H.
  22. Biochem. Pharmacol. v.14 Metabolism of disulfiram and diethyldithiocarbamate in rats with demonstration of an in vivo ethanol-induced inhibition of the glucuronic acid conjugation of the thiol Stromme,J.H.
  23. Science v.216 Human aldehyde dehydrogenase: Mechanism of inhibition by disulfiram Vallari,R.C.;Pietruszko,R.
  24. J. Natl Cancer Inst. v.54 Inhibition of dimethylhydrazine-induced neoplasia of the large intestine by disulfiram Wattenberg,L.M.