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. 1992 Mar;36(3):665–668. doi: 10.1128/aac.36.3.665

Lack of pharmacokinetic interaction between intravenous 2',3'-dideoxyinosine and 3'-azido-3'-deoxythymidine in rats.

M G Wientjes 1, J L Au 1
PMCID: PMC190576  PMID: 1622182

Abstract

We investigated the pharmacokinetic interaction between 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI), given to rats by intravenous injection. For both compounds, the clearances, terminal half-lives, and fractions of the dose excreted unchanged in urine were not altered by the other drug (P greater than 0.05), indicating no pharmacokinetic interaction between the two drugs.

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Selected References

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  1. August E. M., Birks E. M., Prusoff W. H. 3'-Deoxythymidin-2'-ene permeation of human lymphocyte H9 cells by nonfacilitated diffusion. Mol Pharmacol. 1991 Feb;39(2):246–249. [PubMed] [Google Scholar]
  2. Boxenbaum H. G., Riegelman S., Elashoff R. M. Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm. 1974 Apr;2(2):123–148. doi: 10.1007/BF01061504. [DOI] [PubMed] [Google Scholar]
  3. Butler K. M., Husson R. N., Balis F. M., Brouwers P., Eddy J., el-Amin D., Gress J., Hawkins M., Jarosinski P., Moss H. Dideoxyinosine in children with symptomatic human immunodeficiency virus infection. N Engl J Med. 1991 Jan 17;324(3):137–144. doi: 10.1056/NEJM199101173240301. [DOI] [PubMed] [Google Scholar]
  4. Cooney D. A., Ahluwalia G., Mitsuya H., Fridland A., Johnson M., Hao Z., Dalal M., Balzarini J., Broder S., Johns D. G. Initial studies on the cellular pharmacology of 2',3'-dideoxyadenosine, an inhibitor of HTLV-III infectivity. Biochem Pharmacol. 1987 Jun 1;36(11):1765–1768. doi: 10.1016/0006-2952(87)90235-8. [DOI] [PubMed] [Google Scholar]
  5. Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A., Lehrman S. N., Bolognesi D. P., Broder S., Mitsuya H. Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333–8337. doi: 10.1073/pnas.83.21.8333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Griffiths D. A., Hall S. D., Sokol P. P. Interaction of 3'-azido-3'-deoxythymidine with organic ion transport in rat renal basolateral membrane vesicles. J Pharmacol Exp Ther. 1991 Apr;257(1):149–155. [PubMed] [Google Scholar]
  7. Johnson M. A., Fridland A. Phosphorylation of 2',3'-dideoxyinosine by cytosolic 5'-nucleotidase of human lymphoid cells. Mol Pharmacol. 1989 Aug;36(2):291–295. [PubMed] [Google Scholar]
  8. Klecker R. W., Jr, Collins J. M., Yarchoan R., Thomas R., Jenkins J. F., Broder S., Myers C. E. Plasma and cerebrospinal fluid pharmacokinetics of 3'-azido-3'-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther. 1987 Apr;41(4):407–412. doi: 10.1038/clpt.1987.49. [DOI] [PubMed] [Google Scholar]
  9. Knupp C. A., Shyu W. C., Dolin R., Valentine F. T., McLaren C., Martin R. R., Pittman K. A., Barbhaiya R. H. Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin Pharmacol Ther. 1991 May;49(5):523–535. doi: 10.1038/clpt.1991.63. [DOI] [PubMed] [Google Scholar]
  10. Merigan T. C. Treatment of AIDS with combinations of antiretroviral agents. Am J Med. 1991 Apr 10;90(4A):8S–17S. doi: 10.1016/0002-9343(91)90405-m. [DOI] [PubMed] [Google Scholar]
  11. Patel B. A., Chu C. K., Boudinot F. D. Pharmacokinetics and saturable renal tubular secretion of zidovudine in rats. J Pharm Sci. 1989 Jul;78(7):530–534. doi: 10.1002/jps.2600780704. [DOI] [PubMed] [Google Scholar]
  12. Stoeckler J. D., Cambor C., Parks R. E., Jr Human erythrocytic purine nucleoside phosphorylase: reaction with sugar-modified nucleoside substrates. Biochemistry. 1980 Jan 8;19(1):102–107. doi: 10.1021/bi00542a016. [DOI] [PubMed] [Google Scholar]
  13. Wientjes M. G., Au J. L. High-performance liquid chromatographic analysis of 2',3'-dideoxyinosine in biological samples. J Chromatogr. 1991 Feb 15;563(2):400–406. doi: 10.1016/0378-4347(91)80048-h. [DOI] [PubMed] [Google Scholar]
  14. Yarchoan R., Broder S. Development of antiretroviral therapy for the acquired immunodeficiency syndrome and related disorders. A progress report. N Engl J Med. 1987 Feb 26;316(9):557–564. doi: 10.1056/NEJM198702263160925. [DOI] [PubMed] [Google Scholar]
  15. Yarchoan R., Klecker R. W., Weinhold K. J., Markham P. D., Lyerly H. K., Durack D. T., Gelmann E., Lehrman S. N., Blum R. M., Barry D. W. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986 Mar 15;1(8481):575–580. doi: 10.1016/s0140-6736(86)92808-4. [DOI] [PubMed] [Google Scholar]
  16. Yarchoan R., Mitsuya H., Pluda J. M., Marczyk K. S., Thomas R. V., Hartman N. R., Brouwers P., Perno C. F., Allain J. P., Johns D. G. The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS or AIDS-related complex: analysis of activity and toxicity profiles. Rev Infect Dis. 1990 Jul-Aug;12 (Suppl 5):S522–S533. doi: 10.1093/clinids/12.supplement_5.s522. [DOI] [PubMed] [Google Scholar]
  17. Yarchoan R., Pluda J. M., Perno C. F., Mitsuya H., Thomas R. V., Wyvill K. M., Broder S. Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. Ann N Y Acad Sci. 1990;616:328–343. doi: 10.1111/j.1749-6632.1990.tb17853.x. [DOI] [PubMed] [Google Scholar]

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