Chemotherapeutic agents for human immunodeficiency virus infection: Mechanism of action, pharmacokinetics, metabolism, and adverse reactions

Clinical Therapeutics

Volumn 20, Issue 1, 1998, Pages 2-25

  Beach, J Warren ^a  

^a UNIVERSITY OF GEORGIA   (United States)

Author keywords

Acquired immunodeficiency syndrome; Human immunodeficiency virus; Pharmacokinetics; Protease inhibitors; Reverse transcriptase inhibitors

Indexed keywords

ANTIRETROVIRUS AGENT; DELAVIRDINE; DIDANOSINE; INDINAVIR; LAMIVUDINE; NELFINAVIR; NEVIRAPINE; NUCLEOSIDE DERIVATIVE; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; STAVUDINE; ZALCITABINE; ZIDOVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; ARTICLE; DRUG ABSORPTION; DRUG APPROVAL; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG INDUCED DISEASE; DRUG MECHANISM; DRUG METABOLISM; DRUG RESEARCH; DRUG STRUCTURE; FOOD AND DRUG ADMINISTRATION; FOOD DRUG INTERACTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION;

EID: 0031929218     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/S0149-2918(98)80031-3     Document Type: Review

References (108)

1. Klecker RW Jr, Collins JM, Yarchoan R, et al. Plasma and cerebrospinal fluid pharrnacokinetics 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;41:407-412.
2. Yarchoan R, Klecker RW, Weinhold KJ, et al. Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986;1: 575-580.
3. Blum MR, Liao SHT, Good SS, et al. Pharmacokinetics and bioavailability of zidovudine in humans. Am J Med. 1988; 85(Suppl 2A): 189-194.
4. Unadkat JD, Collier AC, Crosby SS, et al. Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal. AIDS. 1990;4:229-232.
5. Crowe S, Cooper DA, Chambers D. Antiretroviral therapies for HIV. Med J Aust. 1996;164:290-295.
6. Gillet JY, Garraffo R, Abrar D, et al. Fetoplacental passage of zidovudine. Lancet. 1989;2:269-270.
7. Retrovir Product Information. Glaxo Wellcome Inc., Research Triangle Park, NC, 1996.
8. Sim SM, Back DJ, Breckenridge AM. The effect of various drugs on the glucuronidation of zidovudine (azidothymidine; AZT) by human liver microsomes. Br J Clin Pharmacol. 1991;32:17-21.
9. Pluda JM, Yarchoan R, Smith PD, et al. Subcutaneous recombinant granulocyte-maerophage colony-stimulating factor used as a single agent and in an alternating regimen with azidothymidine in leukopenic patients with severe human immunodeficiency virus infections. Blood. 1990;76:463-472.
10. Dubin G, Braffman MN. Zidovudine-induced hepatotoxicity. Ann Intern Med. 1989;110:85-86.
11. Shintaku M, Nasu K, Shimizu T. Fulminant hepatic failure in an AIDS patient: Possible zidovudine-induced hepatotoxicity. Am J Gastroenterol. 1993;88:464-466.
12. Don PC, Fusco F, Fried P, et al. Nail dyschromia associated with zidovudine. Ann Intern Med. 1990;112:145-146.
13. Mitsuya H, Weinhold KJ, Furman PA, et al. 3′-azido-3′-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci USA. 1985;82: 7096-7100.
14. Furman PA, Fyte JA, St Clair MH, et al. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci USA. 1986;83:8333-8337.
15. Elwell LP, Ferone R, Freeman GA, et al. Antibacterial activity and mechanism of action of 3′-azido-3′-deoxythymidine (BW A509U). Antimicrob Agents Chemother. 1987;31:274-280.
16. Nakashima H, Matsui T, Harada S, et al. Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III lymphoadenopathy-associated virus by 3′-azido-3′-deoxythymidine in vitro. Antimicrob Agents Chemother. 1986;30:933-937.
17. Larder BA. Viral resistance and the selection of antiretroviral combinations. J Acquired Immune Defic Syndr Hum Retrovirol. 1995;10(Suppl 1):228-233.
18. Lewis LL, Venzon D, Church J, et al. Lamivudine in children with human immunodeficiency virus infection: A phase I/II study. J Infect Dis. 1996;174:16-25.
19. van Leeuwen R, Lange JM, Hussey EK, et al. The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: A phase I study. AIDS. 1992;6:1471-1475.
20. Epivir Product Information. Glaxo Wellcome Inc., Research Triangle Park, NC, 1996.
21. Perry CM, Faulds D, Lamivudine, a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs. 1997;53:657-689.
22. Pluda JM, Cooley TP, Montaner JS, et al. A phase I/II study of 2′-deoxy-3′-thiacytidine (lamivudine) in patients with advanced human immunodeficiency virus infection. J Infect Dis. 1995;171:1438-1447.
23. van Leeuwen R, Katlama C, Kitchen V, et al. Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: A phase I/II study. J Infect Dis. 1995; 171:1166-1171.
24. Hart GJ, Orr DC, Penn CR, et al. Effects of (-)-2′-deoxy-3′-thiacytidine (3TC) 5′-triphosphate on human immunodeficiency virus reverse transcriptase and mammalian DNA polymerases alpha, beta, and gamma. Antimicrob Agents Chemother. 1992;36:1688-1694.
25. Cammack N, Rouse P, Marr CL, et al. Cellular metabolism of (-) enantiomeric 2′-deoxy-3′-thiacytidine. Biochem Pharmacol. 1992;43:2059-2064.
26. Gao Q, Gu Z, Hiscott J, et al. Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2′,3′-dideoxycytidine and 2′,3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother. 1993;37:130-133.
27. Gao Q, Gu Z, Parniak MA, et al. The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2′,3′-dideoxyinosine and 2′,3′-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2′,3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother. 1993;37:1390-1392.
28. Tisdale M, Kemp SD, Parry NR, Larder BA. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci USA. 1993; 90:5653-5656.
29. Schinazi RF, Lloyd RM Jr, Nguyen MH, et al. Characterisation of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob Agents Chemother. 1993;37:875-881.
30. Hartman NR, Yarchoan R, Pluda JM, et al. Pharmacokinetics of 2′,3′-dideoxyadenosine and 2′,3′-dideoxyinosine in patients with severe human immunodeficiency virus infection. Clin Pharmacol Ther. 1990;47:647-654.
31. Knupp CA, Shyu WC, Dolin R, et al. Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin Pharmacol Ther. 1991;49:523-535.
32. Videx Product Information. Bristol-Myers Squibb, Princeton, NJ, 1996.
33. Pelucio MT, Rothenhaus T, Smith M, Ward DJ. Fatal pancreatitis as a complication of therapy for HIV infection. J Emerg Med. 1995;13:633-637.
34. Hartman NR, Yarchoan R, Pluda JM, et al. Pharmacokinetics of 2′,3′-dideoxyinosine in patients with severe human immunodeficiency infection. II. The effects of different oral formulations and the presence of other medications. Clin Pharmacol Ther. 1991;50:278-285.
35. Knupp CA, Milbrath R, Barbhuiyu RH. Effect of time of food administration on the bioavailability of didanosine from a chewable tablet formulation. J Clin Pharmacol. 1993;33:568-573.
36. Kahn J. The clinical use of didanosine. In: Mills J, Volberding PA, Corey L, eds. Antiviral Chemotheraphy. Vol 4. New York: Plenum Press: 1996:245-256.
37. Johnson MA, Fridland A. Phosphorylation of 2′,3′-dideoxyinosine by cytosolic 5′-nucleotidase of human lymphoid cells. Mol Pharmacol. 1989;36:291-295.
38. Ahluwalia G, Cooney DA, Mitsuya H. Initial studies on the cellular pharmacology of 2′,3′-dideoxyinosine, an inhibitor of HIV infectivity. Biochem Pharmacol. 1987;36:3797-3800.
39. Johnson MA, Ahluwalia G, Connelly MC, et al. Metabolic pathways for the activation of the antiretroviral agent 2′,3′-dideoxyadenosine in human lymphoid cells. J Biol Chem. 1988;263:15354-15357.
40. Kozal MJ, Kroodsman K, Winters MA, et al. Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. Ann Intern Med. 1994;121:263-268.
41. Yarchoan R, Lietzau JA, Nguyen BY, et al. A randomized pilot study of alternating or simultaneous zidovudine and didanosine therapy in patients with symptomatic human immunodeficiency virus infection. J Infect Dis. 1994;169:9-17.
42. Klecker RW, Collins JM, Yarchoan RC, et al. Pharmacokinetics of 2′,3′-dideoxycytidine in patients with AIDS and related disorders. J Clin Pharmacol. 1988;28: 837-842.
43. Gustavson LE, Fukuda EK, Rubio FA, Dunton AW. A pilot study of the bioavailability and pharmacokinetics of 2′,3′-dideoxycytidine in patients with AIDS or AIDS-related complex. J Acquired Immune Defic Syndr Hum Retrovirol. 1990; 3:28-31.
44. Hivid Product Information. Roche Laboratories Inc., Nutley, NJ, 1995.
45. Broder S. Pharmacodynamics of 2′,3′-dideoxycytidine: An inhibitor of human immunodeficiency virus. Am J Med. 1990; 88(Suppl 5B):2S-7S.
46. Yarchoan R, Perno CF, Thomas RV, et al. Phase I studies of 2′,3′-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet. 1988;1: 76-81.
47. Blum AS, Dal Pan GJ, Feinberg J, et al. Low-dose zalcitabine-related toxic neuropathy: Frequency, natural history, and risk factors. Neurology. 1996;46:999-1003.
48. Starnes MC, Cheng Y-C. Cellular metabolism of 2′,3′-dideoxycytidine, a compound active against human immunodeficiency virus in vitro. J Biol Chem. 1987; 262:988-991.
49. Cooney DA, Dalal M, Mitsuya H, et al. Initial studies on the cellular pharmacology of 2′,3′-dideoxycytidine, an inhibitor of HTLV-III infectivity. Biochem Pharmacol. 1986;65:2065-2068.
50. Chen C-H, Cheng Y-C. Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2′,3′-dideoxycytidine. J Biol Chem. 1989;264: 11934-11937.
51. Dudley MN, Graham KK, Kaul S, et al. Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex. J Infect Dis. 1992; 166:480-485.
52. Browne MJ, Mayer KH, Chafee SB, et al. 2′,3′-didehydro-3′-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: A phase I trial. J Infect Dis. 1993;167:21-29.
53. Kline MW, Dunkle LM, Church JA, et al. A phase I/II evaluation of stavudine (d4T) in children with human immunodeficiency virus infection. Pediatrics. 1995;96:247-252.
54. Zerit Product Information. Bristol-Myers Squibb, Princeton, NJ, 1996.
55. Ho HT, Hitchcock MJM. Cellular pharmacology of 2′,3′-dideoxy-2′,3′-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus. Antimicrob Agents Chemother. 1989;33: 844-849.
56. Martin JC, Hitchcock MJM, Fridland A, et al. Comparative studies of 2′,3′-didehydro-2′,3′-dideoxythymidine (D4T) with other pyrimidine nucleoside analogues. Ann NY Acad Sci. 1990;616:22-28.
57. Balzarini J, Herdewijn P, De Clercq E. Differential patterns of intracellular metabolism of 2′,3′-didehydro-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. J Biol Chem. 1989;264:6127-6133.
58. Mansuri MM, Hitchcock MJM, Buroker RA, et al. Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs against human immunodeficiency virus. Antimicrob Agents Chemother. 1990;34:637-641.
59. Sommadossi JP, Carlisle R, Zhu Z. Cellular pharmacology of 3′-azido-3′-deoxythymidine, with evidence of incorporation into DNA of human bone marrow cells. Mol Pharmacol. 1989;36:9-14.
60. Zhu Z, Hitchcock MJM, Sommadossi JP. Metabolism and DNA interaction of 2′,3′-didehydro-2′,3′-dideoxythymidine in human bone marrow cells. Mol Pharmacol. 1991;40:838-845.
61. Viramune Product Information. Roxane Laboratories, Columbus, Ohio, 1996.
62. Cheeseman SH, Hattox SE, McLaughlin MM, et al. Pharmacokinetics of nevirapine: Initial single-rising-dose study in humans. Antimicrob Agents Chemother. 1993;37:178-182.
63. Cheeseman SH, Havlir D, McLaughlin MM, et al. Phase I/II evaluation of nevirapine alone and in combination with zidovudine for infection with human immunodeficiency virus. J Acquired Immune Defic Syndr Hum Retrovirol. 1995;8: 141-151.
64. Luzuriaga K, Bryson Y, McSherry G, et al. Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children. J Infect Dis. 1996;174:713-721.
65. Richman DD, Rosenthal AS, Skoog M, et al. BI-RG-587 is active against zidovudine-resistant human immunodeficiency virus type 1 and synergistic with zidovudine. Antimicrob Agents Chenwther. 1991; 35:305-308.
66. Grob PM, Wu JC, Cohen KA, et al. Non-nucleoside inhibitors of HIV-1 reverse transcriptase: Nevirapine as a prototype drug. AIDS Res Hum Retroviruses. 1992; 8:145-152.
67. Kopp EB, Miglietta JJ, Shrutkowski AG, et al. Steady state kinetics and inhibition of HIV-1 reverse transcriptase by a non-nucleoside dipyridodia/epinone BI-RG-587, using a heteropolymeric template. Nucleic Acids Res. 1991;19:3035-3039.
68. Koup RA, Merluzzi VJ, Hargrave KD, et al. Inhibition of human immunodeficiency virus type 1 (HIV-1 replication by the dipyridodiazepinone BI-RG-587. J Infect Dis. 1991;163:966-970.
69. Cohen KA, Hopkins J, Ingraham RH, et al. Characterization of the binding site for nevirapine (BI-RG-587), a nonnucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. J Biol Chem. 1991;266:14670-14674.
70. Wu JC, Warren TC, Adams J, et al. A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a non-substrate binding site. Biochemistry. 1991; 30:2022-2026.
71. Richman DD, Havlir D, Corbeil J, et al. Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J Virol. 1994;68:1660-1666.
72. Richman DD. HIV drug resistance. AIDS Res Hum Retroviruses. 1992;8:1065-1071.
73. Rescriptor Product Information. Pharmacia & Upjohn Company, Kalamazoo, Mich, 1997.
74. Davey RT Jr, Chaitt DG, Reed GF, et al. Randomized, controlled phase I/II trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 1996;40:1657-1664.
75. Freimuth WW. Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. In: Mills J, Volberding PA, Corey L. eds. Antiviral Chemotherapy. Vol 4. New York: Plenum Press; 1996: 279-289.
76. Morse GD, Fischle MA, Shelton MJ, et al. Single dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infections. Antimicrob Agents Chemother. 1997;41:169-174.
77. Chaput AJ, D'Ambrosio R, Morse GD. In vitro protein-binding characteristics of delavirdine and its N-dealkylated metabolite. Antiviral Res. 1996;32:81-89.
78. Staton BA, Johnson MG, Friis JM, Adams WJ. Simple, rapid and sensitive high-performance liquid chromatographic determination of delavirdine and its N-deisopropyl metabolite in human plasma. J Chromatogr B Biomed Appl. 1995;668: 99-106.
79. Dueweke TJ, Poppe SM, Romero DL, et al. U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother. 1993; 37:1127-1131.
80. Chong KT, Pagano PJ, Hinshaw RR. Bisheteroarylpiperazine reverse transcriptase inhibitor in combination with 3′-azido-3′-deoxythymidine or 2′,3′-dideoxycytidine synergistically inhibits human immunodeficiency virus type I replication in vitro. Antimicrob Agents Chemother. 1994;38:288-293.
81. Coleman R. Overview of antiretroviral therapy. Pharmacotherapy. 1994;14(Suppl): 3S-8S.
82. Nagy K, Young M, Baboonian C, et al. Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in a single cycle of infection: Evidence for a role of protease in the early phase. J Virol. 1994;68:757-765.
83. Craig JC, Duncan IB, Hockley D, et al. Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) protease. Antiviral Res. 1991;16: 295-305.
84. Johnson MA, Merrill DP, Chou TC, Hirsh MS. Human immunodeficiency virus type 1 (HIV-1) inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2′,3′-dideoxycytidine, or recombinant interferon-alpha A against zidovudine-sensitive or -resistant HIV-1 in vitro. J Infect Dis. 1992;166:1143-1146.
85. Wlodawer A. Rational drug design: The proteinase inhibitors. Pharmacotherapy. 1994;14(Suppl):9S-20S.
86. Kitchen VS, Skinner C, Ariyoshi K, et al. Safety and activity of saquinavir in HIV infection. Lancet. 1995;345:952-955.
87. Noble S, Faulds D. Saquinavir: A review of its pharmacology and clinical potential in the management of HIV infection. Drugs. 1996;52:93-112.
88. Invirase Product Information. Roche Laboratories Inc., Nutley, NJ, 1996.
89. Fortovase Product Information. Roche Laboratories Inc., Nutley, NJ, 1996.
90. Markowitz M, Saag M, Powderly WG, et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. NEJM. 1995;333:1534-1539.
91. Norvir Product Information. Abbott Laboratories, Abbott Park, Ill, 1997.
92. Kempf DJ, Marsh KC, Denissen JF, et al. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc Natl Acad Sci USA. 1995;92:2484-2488.
93. Danner SA, Carr A, Leonard JM, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. NEJM. 1995; 333:1528-1533.
94. Hsu A, Granneman R, Witt G, et al. Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus infected subjects. Antimicrob Agents Chemother. 1997;41:898-905.
95. Moyle G, Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs. 1996;51:701-712.
96. Crixivan Product Information. Merck & Co., Inc., West Point, Pa, 1997.
97. Lin JH, Chen IW, Vastag KJ, Ostovic D. pH-dependent oral absorption of L-735,524, a potent HIV protease inhibitor, in rats and dogs. Drug Metab Dispos. 1995;23:730-735.
98. Kwei GY, Novak LB, Hettrick LA, et al. Regiospecific intestinal absorption of the HIV protease inhibitor L-735,524 in beagle dogs. Pharm Res. 1995;12:884-888.
99. Lin JH, Chiba M, Balani SK, et al. Species differences in the pharmacokinetics and metabolism of indinavir, a potent human immunodeficiency virus protease inhibitor. Drug Metab Dispos. 1996;24: 1111-1120.
100. Chiba M, Hensleigh M, Nishime JA, et al. Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor. Drug Metab Dispos. 1996;24: 307-314.
101. Balani SK, Arison BH, Mathai L, et al. Metabolites of L-735,524, a potent HIV-1 protease inhibitor, in human urine. Drug Metab Dispos. 1995;23:266-270.
102. Balani SK, Woolf EJ, Hoagland VL, et al. Disposition of indinavir, a potent HIV-1 protease inhibitor after an oral dose in humans. Drug Metab Dispos. 1996;24: 1389-1394.
103. Condra JH, Holder DJ, Schleif WA, et al. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor. J Virol. 1996;70:8270-8276.
104. Reich SH, Melnick M, Davies JF, et al. Protein structure-based design of potent orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease. Proc Natl Acad Sci USA. 1995; 92:3298-3302.
105. Viracept Product Information. Agouron Pharmaceuticals, Inc., La Jolla, Calif. 1997.
106. Shetty BV, Kosa MB, Khalil DA, Webber S. Preclinical pharmacokinetics and distribution to tissue of AG1343, an inhibitor of human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 1996;40:110-114.
107. Pantaleo G, Graziosi C, Demarest JF, et al. HIV infection is active and progressive in lymphoid tissue during clinically latent stage of disease. Nature. 1993;362: 355-358.
108. Patrick AK, Mo H, Markowitz M, et al. Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Antimicrob Agents Chemother. 1996;40:292-297.