Disposition of [1′-14C]stavudine after oral administration to humans

Drug Metabolism and Disposition

Volumn 38, Issue 4, 2010, Pages 655-666

  Zhou, Lian ^a   Kaul, Sanjeev ^a   Liu Kreyche, Peggy ^a   Tran, Scott B ^a   Espina, Robert R ^a,b   Warrack, Bethanne M ^a   Roongta, Vikram A ^a   Iyer, Ramaswamy A ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2',3' DIDEHYDRODIDEOXYRIBOSE; 2',3' DIDEOXY 3' GLUTATHIONE RIBOSE; 3' GLUTATHIONE RIBOSE; ACETYLCYSTEINE; CYTOCHROME P450; DEOXYRIBOSE; DRUG METABOLITE; GLUCURONIDE; GLUTATHIONE; GLYCOSIDE; RIBOSE; STAVUDINE; UNCLASSIFIED DRUG; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BIOTRANSFORMATION; CLINICAL TRIAL; CONJUGATE; CONTROLLED STUDY; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG FECES LEVEL; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG OXIDATION; DRUG TISSUE LEVEL; DRUG URINE LEVEL; HUMAN; HUMAN EXPERIMENT; LIVER MICROSOME METABOLISM; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; NORMAL HUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RADIOACTIVITY; RAT; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TISSUE DISTRIBUTION; ANIMAL; CHEMISTRY; FECES; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROLYSIS; IN VITRO STUDY; ISOTOPE LABELING; LIVER MICROSOME; LONG EVANS RAT; MASS SPECTROMETRY; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; ORAL DRUG ADMINISTRATION;

RATTUS;

ADMINISTRATION, ORAL; ANIMALS; ANTI-HIV AGENTS; AREA UNDER CURVE; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FECES; HUMANS; HYDROLYSIS; ISOTOPE LABELING; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MICROSOMES, LIVER; RATS; RATS, LONG-EVANS; RIBOSE; STAVUDINE; TISSUE DISTRIBUTION;

EID: 77950279895     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.109.030239     Document Type: Article

References (19)

1. Balzarini J (1994) Metabolism and mechanism of antiretroviral action of purine and pyrimidine derivatives. Pharm World Sci 16:113-126.
2. Blair IA (2006) Endogenous glutathione adducts. Curr Drug Metab 7:853-872.
3. Cretton EM, Zhou Z, Kidd LB, McClure HM, Kaul S, Hitchcock MJ, and Sommadossi JP (1993) In vitro and in vivo disposition and metabolism of 3′-deoxy-2′,3′-didehydrothymidine. Antimicrob Agents Chemother 37:1816-1825.
4. 14C]stavudine (d4T). J Labelled Comp Rad 38:614-623.
5. Grasela DM, Stoltz RR, Barry M, Bone M, Mangold B, O'Grady P, Raymond R, and Haworth SJ (2000) Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis. Antimicrob Agents Chemother 44:2149-2153.
6. Griffith OW (1986) Beta-amino acids: mammalian metabolism and utility as alpha-amino acid analogues. Annu Rev Biochem 55:855-878.
7. Huang P, Farquhar D, and Plunkett W (1992) Selective action of 2′,3′-didehydro-2′,3′-dideoxythymidine triphasphate on human immunodeficiency virus reverse transcriptase and human DNA polymerases. J Biol Chem 267:2817-2822.
8. Institute of Laboratory Animal Resources (1996) Guide for the Care and Use of Laboratory Animals, 7th ed. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, Washington DC.
9. International Commission on Radiological Protection (2008) Publication 103: Recommendations of the ICRP, Elsevier, Philadelphia.
10. Kaul S and Dandekar KA (1993) Pharmacokinetics of the anti-human immunodeficiency virus nucleoside analog stavudine in cynomolgus monkeys. Antimicrob Agents Chemother 37: 1160-1162.
11. Kaul S, Dandekar KA, Schilling BE, and Barbhaiya RH (1999) Toxicokinetics of 2′,3′-didehydro-3′-deoxythymidine, stavudine (D4T). Drug Metab Dispos 27:1-12.
12. Lea AP and Faulds D (1996) Stavudine: a review of its pharmacodynamic and pharmacokinetic properties and clinical potential in HIV infection. Drugs 51:846-864.
13. Moran LA, Scrimgeour KG, Horton HR, and Rawn JD (1994) Biochemistry, pp 22.26 -22.27, Neil Patterson, Englewood Cliffs, NJ.
14. Niemann MA and Berech J Jr (1981) Thymidine catabolism and the reutilization of its degradative products in Tetrahymena pyriformis. Metabolism of [2,6-14C2]thymidine and [2-14C]methylmalonic acid. Biochim Biophys Acta 652:347-353.
15. Russell JW, Whiterock VJ, Marrero D, and Klunk LJ (1990) Disposition in animals of a new anti-HIV agent: 2′,3′-didehydro-3′- deoxythymidine. Drug Metab Dispos 18:153-157.
16. Schaad HJ, Petty BG, Grasela DM, Christofalo B, Raymond R, and Stewart M (1997) Pharmacokinetics and safety of a single dose of stavudine (d4T) in patients with severe hepatic impairment. Antimicrob Agents Chemother 41:2793-2796.
17. Shapiro R and Danzig M (1972) Acid hydrolysis of deoxycytidine and deoxyuridine derivatives. The general mechanism of deoxyribonucleoside hydrolysis. Biochemistry 11:23-29.
18. Siegfried NL, Van Deventer PJ, Mahomed FA, and Rutherford GW (2006) Stavudine, lamivudine and nevirapine combination therapy for treatment of HIV infection and AIDS in adults. Cochrane Database Syst Rev 2:CD004535.
19. Zhu M, Zhao W, Vazquez N, and Mitroka JG (2005) Analysis of low level radioactive metabolites in biological fluids using high-performance liquid chromatography with microplate scintillation counting: method validation and application. J Pharm Biomed Anal 39:233-245.