Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations

Clinical Pharmacokinetics

Volumn 32, Issue 3, 1997, Pages 194-209

  Barry, Michael ^a   Gibbons, Sara ^a   Back, David ^a   Mulcahy, Fiona ^b  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b ST JAMES S HOSPITAL   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; ANTIVIRUS AGENT; COTRIMOXAZOLE; DAPSONE; DIDANOSINE; INDINAVIR; NUCLEOSIDE ANALOG; OROSOMUCOID; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; ZALCITABINE; ZIDOVUDINE;

ANTIVIRAL ACTIVITY; DISEASE COURSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG RESISTANCE; ENZYME INDUCTION; ENZYME INHIBITION; FOOD INTAKE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MORTALITY; PRIORITY JOURNAL; REVIEW; STOMACH PH; VIRION;

EID: 0030895312     PISSN: 03125963     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003088-199732030-00003     Document Type: Review

References (124)

1. Fischl MA, Richman DD, Grieco MH, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1987; 317: 185-91
2. Fischl MA, Richman DD, Hansen N, et al. The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. Ann Intern Med 1990; 112: 727-37
3. Hamilton JD, Hartigan PM, Simberkoff MS, et al. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. N Engl J Med 1992; 326: 437-43
4. Concorde Coordinating Committee. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 1994; 343: 871-81
5. Cooper DA, Gatell JM, Kroon S, et al. Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. N Engl J Med 1993; 329: 297-303
6. Mulder JW, Cooper DA, Methiesen L, et al. Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. AIDS 1994; 8: 313-21
7. Volberding P, Lagakos SW, Koch MA, et al. Zidovudine in asymptomatic human immunodeficiency virus. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimetre. N Engl J Med 1990; 322: 941-9
8. Larder BA, Darby G, Richman DD. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 1989; 243: 1731-4
9. Japour AJ, Welles S, D'Aquila RT, et al. Prevalence and clinical significance of zidovudine resistance mutations in human immunodeficiency virus isolates from patients after long-term zidovudine treatment. J Infect Dis 1995; 171: 1172-9
10. Montaner JSG, Singer J, Schechter MT, et al. Clinical correlates of in vitro HIV-1 resistance to zidovudine: results of the multicentre Canadian AZT trial. AIDS 1993; 7: 189-96
11. Choo V. Combination superior to zidovudine in Delta trial. Lancet 1995; 346: 895
12. Montaner JSG, Schechter MT. A year of transformation in HIV/AIDS. Lancet 1995; 346 Suppl.: 12
13. Delta Coordinating Committee. Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet 1996; 348: 283-91
14. Collier AC, Coombs RW, Schoenfeld DA, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine and zalcitabine. N Engl J Med 1996; 334: 1011-7
15. Debouck C. The HIV-1 protease as a therapeutic target for AIDS. AIDS Res Hum Retrovir 1992; 8: 153-64
16. Markowitz M, Saag M, Powderly WG, et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease to treat HIV-1 infection. N Engl J Med 1995; 333: 1534-9
17. Roberts NA. Drug resistance patterns of saquinavir and other HIV proteinase inhibitors. AIDS 1995; 9 Suppl. 2: 27-32
18. Condra JH, Schleif WA, Blahy OM, et al. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995; 374: 569-71
19. Richman DD. Protease uninhibited. Nature 1995; 374: 494
20. 2 symmetry-based human immunodeficiency virus protease inhibitor. Antimicrob Agents Chemother 1995; 39: 1559-64
21. Kitchen VS, Skinner C, Ariyoshi K, et al. Safety and activity of saquinavir in HIV infection. Lancet 1995; 345: 952-5
22. Moyle G, Gazzard B. Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs 1996; 51: 701-12
23. 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: 2484-8
24. Lake-Bakaar G, Tom W, Lake-Bakaar D, et al. Gastropathy and ketoconazole metabolism in the acquired immunodeficiency syndrome. Ann Intern Med 1988; 109: 471-3
25. Welage LS, Carver PL, Revankar S, et al. Alterations in gastric acidity in patients infected with human immunodeficiency virus. Clin Infect Dis 1995; 21: 1431-8
26. Blum RA, D'Andrea DT, Florentino BM, et al. Increased gastric pH and the bioavailability of fluconazole and ketoconazole. Ann Intern Med 1991; 114: 755-7
27. Tam YK. Individual variation in first-pass metabolism. Clin Pharmacokinet 1993; 25: 300-28
28. Semple HA, Tam YK, Coutts RT. A computer simulation of the food effect: transient changes in hepatic blood flow and Michaelis-Menten parameters as mediators of hepatic first pass metabolism and bioavailability of propranolol. Biopharm Drug Dispos 1990; 11: 61-76
29. Muirhead GJ, Shaw T, Williams PEO, et al. Pharmacokinetics of the HIV-proteinase inhibitor, Ro 318959, after single and multiple oral doses in healthy volunteers. Br J Clin Pharmacol 1992; 34: 170P
30. Friedman S. Clinical manifestations of HIV disease: gastrointestinal and hepatobiliary aspects. In: Cohen PT, Sande MA, Volberding PA, editors. The AIDS knowledge base. New York: Little, Brown & Co., 1995: 5.20-7
31. Kotler DP, Gaetz HP, Lange M, et al. Enteropathy associated with the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101: 421-8
32. Gillin JS, Shike M, Alcode N. Malabsorption and mucosal abnormalities of the small intestine in the acquired immunodeficiency syndrome. Ann Intern Med 1985; 102: 619-22
33. Smith PD, Lane HC, Gill VJ. Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS): etiology and response to therapy. Ann Intern Med 1988; 108: 328-33
34. McLean A, Morgan DJ. Clinical pharmacokinetics in patients with liver disease. Clin Pharmacokinet 1991; 21: 42-69
35. Cappell MS. Hepatobiliary manifestations of the acquired immunodeficiency syndrome. Am J Gastroenterol 1991; 86: 1-15
36. Lebovics E, Thung SN, Schaffner F, et al. The liver in the acquired immunodeficiency syndrome: a clinical and histological study. Hepatology 1985; 5: 293-8
37. Schneiderman DJ, Arenson DH, Cello JP, et al. Hepatic disease in patients with the acquired immunodeficiency syndrome (AIDS). Hepatology 1987; 7: 925-30
38. Glasgow BJ, Anders K, Layfield LJ, et al. Clinical and pathological findings of the liver in the acquired immunodeficiency syndrome (AIDS). Am J Clin Pathol 1985; 83: 582-8
39. Sonnerborg A, Abebe A, Strannegard O. Hepatitis C virus infection in individuals with and without human immunodeficiency virus type 1 infection. Infection 1990; 18: 347-51
40. Housset C, Pol S, Carnot F, et al. Interactions between human immunodeficiency virus-1, hepatitis delta virus and hepatitis B infections in 260 chronic carriers of hepatitis B virus. Hepatology 1992; 15: 578-83
41. McNair AN, Main J, Thomas HC. Interactions of HIV and the hepatotropic viruses. Semin Liver Dis 1992; 12: 188-96
42. Sotaniemi EA, Rautio A, Bäckstrom M, et al. CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney disease and epileptic patients. Br J Clin Pharmacol 1995; 39: 71-6
43. du Souich P, Verges J, Erill S. Plasma protein binding and pharmacological response. Clin Pharmacokinet 1993; 24: 435-40
44. Rowland M, Tozer TN. Distribution: clinical pharmacokinetics, concepts and applications. London: Williams & Wilkins, 1995: 137-55
45. Roultledge PA. The plasma protein binding of basic drugs. Br J Clin Pharmacol 1986; 22: 499-506
46. Kageyama SS, Anderson BD, Hoesterey BL, et al. Protein binding of human immunodeficiency virus protease inhibitor KN1-272 and alteration of its in vitro antiretroviral activity in the presence of high concentration proteins. Antimicrob Agents Chemother 1994; 38: 1107-11
47. Livingstone DJ, Pazhanisamy S, Porter DJT, et al. Weak binding of VX-478 to human plasma proteins and implications for anti-human immunodeficiency virus therapy. J Infect Dis 1995; 172: 1238-45
48. 1-acid glycoprotein as markers of inflammation and cancer. Glycoconj J 1995; 12: 241-7
49. Oie S, Jacobson MA, Abrams DI. Alpha 1-acid glycoprotein levels in AIDS patients before and after short term treatment with zidovudine (ZDV). J Acquir Immune Defic Syndr Hum Retrovirol 1993; 5: 531-3
50. 1-Acid glycoprotein (orosomucoid): pathophysiological changes in glycosylation in relation to its function. Glycoconj J 1995; 12: 227-33
51. 1-acid glycoprotein. J Infect Dis 1995; 171: 546-51
52. 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. N Engl J Med 1995; 333: 1528-33
53. Koch-Weser J, Seller EM. Binding of drugs to serum albumin. N Engl J Med 1976; 294: 526-31
54. Rolan PE. Plasma protein binding displacement interactions: why are they still regarded as clinically important? Br J Clin Pharmacol 1994; 37: 125-8
55. Sansom LN, Evans AM. What is the true clinical significance of plasma protein binding displacement interactions? Drug Saf 1995; 12: 227-33
56. Schary WL, Lewis RJ, Rowland M. Warfarin-phenylbutazone interaction in man: a long term multiple dose study. Res Commun Chem Pathol Pharmacol 1975; 10: 633-72
57. Banfield C, O'Reilly RO, Chan E, et al. Phenylbutazone-warfarin interaction in man: further stereochemical and metabolic considerations. Br J Clin Pharmacol 1983; 16: 669-75
58. Morgan DJ, Smallwood RA. Clinical significance of pharmacokinetic models of hepatic elimination. Clin Pharmacokinet 1990; 18: 61-76
59. Rowland M, Tozer TN, editors. Interacting drugs in clinical pharmacokinetics: concepts and applications. Philadelphia: Williams & Wilkins, 1995: 267-89
60. Hansen JM, Christensen LK. Drug interactions with oral sulphenylurea hypoglycaemic drugs. Drugs 1977; 13: 24-34
61. Steigbigel RT, Berry P, Mellors J, et al. Efficacy and safety of the HIV protease inhibitor indinavir sulfate (MK639) at escalating dose [abstract no. 146]. Retrovirus Conference; 1996 Jan; Washington, DC
62. Back DJ, Rogers SM. First pass metabolism by gastrointestinal mucosa. Aliment Pharmacol Ther 1987; 1: 339-57
63. Wrighton SA, Steven JC. The human hepatic cytochromes P450 involved in drug metabolism. Crit Rev Toxicol 1992; 22: 1-21
64. Kempf D, Marsh K, Denissen J, et al. Coadministration with ritonavir enhances the plasma levels of HIV protease inhibitors by inhibition of cytochrome P450 [abstract no 143]. Retrovirus Conference; 1996 Jan; Washington, DC
65. Barry M, Feely J. Enzyme induction and inhibition. Pharmacol Ther 1990; 48: 71-94
66. Waxman DJ, Azarnoff L. Phenobarbitone induction of cytochrome P-450 gene expression. Biochem J 1992; 281: 577-92
67. De Cock KM, Grant A, Porter JDH. Preventive therapy for tuberculosis in HIV-infected persons: international recommendations, research and practice. Lancet 1995; 345: 833-6
68. Selwyn PA, Hartel D, Lewis VA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989; 320: 545-50
69. Buehler JW, Ward JW. A new definition for AIDS surveillance. Ann Intern Med 1993; 118: 390-2
70. Barnes PF, Bloch AB, Davidson PT, et al. Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 1991; 324: 1644-50
71. Ormerod LP. Guidelines on the management of tuberculosis and HIV infection in the United Kingdom. BMJ 1992; 304: 1231-3
72. Venkateran K. Pharmacokinetic drug interactions with rifampicin. Clin Pharmacokinet 1992; 22: 47-65
73. Park BK, Breckenridge AM. Clinical implications of enzyme induction and enzyme inhibition. Clin Pharmacokinet 1981; 6: 1-24
74. Teunissen MWE, Bakker W, Meerburg-Van Der Torren JE, et al. Influence of rifampicin treatment on antipyrine clearance and metabolite formation in patients with tuberculosis. Br J Clin Pharmacol 1984; 18: 701-6
75. Horsburgh CR. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324: 1332-8
76. Havelik JA, Horsburgh CR, Mitchock B, et al. Disseminated Mycobacterium avium complex infection: clinical identification and epidemiological trends. J Infect Dis 1992; 165: 577-80
77. Masur H. Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. N Engl J Med 1993; 329: 898-904
78. Nightingale SD, Cameron DW, Gordin FM, et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 1993; 329; 828-33
79. Di Pietro N, Kamal M. Rifabutin for the prevention of Mycobacterium avium complex bacteraemia in AIDS and HIV positive patients with CD4 counts ≤200 cells/μl. Clin Drug Invest 1996; 11: 1-10
80. Skinner MH, Blaschke TF. Clinical pharmacokinetics of rifabutin. Clin Pharmacokinet 1995; 28: 115-25
81. Breckenridge AM, Orme ML'E. Clinical implications of enzyme induction. Ann NY Acad Sci 1971; 179: 421-31
82. Patsalos PN, Duncan JS, Sharvon SD. Effect of the removal of individual antiepileptic drugs on antipyrine kinetics in patients taking polytherapy. Br J Clin Pharmacol 1988; 26: 253-9
83. So YT, Beckstead JH, Davis RL. Primary central nervous system lymphoma in acquired immunodeficiency syndrome: a clinical and pathological study. Ann Neurol 1986; 20: 566-72
84. Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med 1992; 327: 1643
85. Ducharme MP, Slaughter RL, Warbasse LH, et al. Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin. Clin Pharmacol Ther 1995; 58: 617-24
86. Haria M, Bryson HM, Goa KL. Itraconazole: a reappraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections. Drugs 1996; 51: 585-620
87. Ouellet D, Hsu A, Qian J, et al. Effect of ritonavir on the pharmacokinetics of ethinyl estradiol in healthy female volunteers [abstract Mo. B. 1198]. XI International Conference on AIDS; 1996 Jul 7-12; Vancouver
88. Hsu A, Granneman GR, Sun E, et al. Assessment of single and multiple dose interactions between ritonavir and saquinavir [abstract LB. B. 6041]. XI International Conference on AIDS; 1996 Jul 9-12; Vancouver
89. Merry C, Barry M, Mulcahy F, et al. Saquinavir pharmacokinetics alone and in combination with ritonavir in patients with HIV disease. AIDS 1996; 10 Suppl. 2: 13
90. Keogh A, Spratt P, McCosker C, et al. Ketoconazole to reduce the need for cyclosporin after cardiac transplantation. N Engl J Med 1995; 333: 628-33
91. Back DJ, Tjia JF. Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporine by human liver microsomes. Br J Clin Pharmacol 1991; 32: 624-6
92. Ouellet D, Hsu A, Granneman GR, et al. Assessment of the pharmacokinetic interaction between ritonavir and clarithromycin [abstract PI 58]. Clin Pharmacol Ther 1996; 59: 143
93. Olkkola KT, Aranko K, Laorila H, et al. A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 1993; 53: 298-305
94. Cato A, Cavanaugh JH, Shi H, et al. Assessment of multiple doses of ritonavir on the pharmacokinetics of rifabutin [abstract Mo. B. 1199]. XI International Conference on AIDS; 1996 Jul 7-12; Vancouver
95. Kumar GN, Rodrigues AD, Buko AM, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Ex Ther 1996 Apr; 277: 423-31
96. Bertz RJ, Cao G, Cavanaugh JH, et al. Effect of ritonavir on the pharmacokinetics of desipramine [abstract Mo. B. 1201]. XI International Conference on AIDS; 1996 Jul 7-12; Vancouver
97. Hughes WT, Kennedy W, Dugdale M, et al. Prevention of Pneumocystis carinii pneumonitis in AIDS patients with weekly dapsone. Lancet 1990; 336: 1066
98. Vöhringer H-F, Arastéh K. Pharmacokinetic optimisation in the treatment of Pneumocystis carinii pneumonia. Clin Pharmacokinet 1993; 24: 388-412
99. Masur H. Prevention and treatment of Pneumocystis carinii pneumonia. N Engl J Med 1992; 327: 1853
100. Coleman MD, Breckenridge AM, Park BK. Bioactivation of dapsone to a cytotoxic metabolite by human hepatic microsomal enzymes. Br J Clin Pharmacol 1989; 28: 389-95
101. Uetrecht JP, Zahid N, Shear NH, et al. Metabolism of dapsone to a hydroxylamine by human neutrophils and mononuclear cells. J Pharmacol Exp Ther 1988; 245: 274-9
102. Fleming CM. Human liver microsomal N-hydroxylation of dapsone by cytochrome P450 3A4. Mol Pharmacol 1992; 41: 975-80
103. Gill HJ, Tingle MD, Park K. N-Hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity. Br J Clin Pharmacol 1995; 40: 531-8
104. Coleman MD, Scott AK, Breckenridge AM, et al. The use of cimetidine as a selective inhibitor of dapsone N-hydroxylation in man. Br J Clin Pharmacol 1990; 30: 761-7
105. Rhodes LE, Tingle MD, Park BK, et al. Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy. Br J Dermatol 1995; 132: 257-62
106. Hardy WD, Feinberg J, Finkelstein DM, et al. A controlled trial of trimethoprim-sulphamethoxazole or aerosolised pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med 1992; 327: 1842-8
107. Smith D, Gazzard B. Treatment and prophylaxis of Pneumocystis carinii pneumonia in AIDS patients. Drugs 1991; 42: 628-39
108. Van der Ven AJAM, Koopmans PP, Vree TB, et al. Adverse reactions to co-trimoxazole in HIV infection. Lancet 1991; 338: 431-3
109. Schneider MME, Hoepelman AIM, Eeftinck-Schattenkerk JKM, et al. A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. N Engl J Med 1992; 327: 1836-41
110. Reider MJ, Uetrecht J, Shear NH, et al. Synthesis and in vitro toxicity of hydroxylamine metabolites of sulphonamides. J Pharmacol Exp Ther 1988; 244: 724-8
111. 4-Hydroxylation of sulfamethoxazole by cytochrome P-450 of the cytochrome P450 2C subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat hepatic microsomes. Drug Metab Dispos 1995; 23: 406-14
112. Mitra AK, Thummel KE, Kalhorn TF, et al. Inhibition of sulphamethoxazole hydroxylamine formation by fluconazole in human liver microsomes and healthy volunteers. Clin Pharmacol Ther 1996; 59: 332-40
113. Gill HJ, Maggs JL, Madden S, et al. The effect of fluconazole and ketoconazole on the metabolism of sulphamethoxazole in man. Br J Clin Pharmacol 1996; 42: 347-53
114. Rieder MJ, Krause R, Bird IA, et al. Sulfonamide toxicity in HIV infection. Clin Pharmacol Ther 1994; 55: 181
115. Meekins CV, Sullivan TJ, Gruchalla RS. Immunochemical analysis of sulfonamide drug allergy: identification of sulfamethoxazole-substituted human serum proteins. J Allergy Clin Immunol 1994; 94: 1017-24
116. Bertz RJ, Cao G, Cavanaugh JH, et al. Effect of ritonavir on the pharmacokinetics of trimethoprim/sulphamethoxazole [abstract Mo. B. 1197]. XI International Conference on AIDS; 1996 Jul 7-12; Vancouver
117. Morse GD, Shelton MJ, O'Donnell AM. Comparative pharmacokinetics of antiviral nucleoside analogues. Clin Pharmacokinet 1993; 24: 101-23
118. Back DJ, Ormesher S, Tjia JF, et al. Metabolism of 2′,3′-dideoxyinosine (ddI) in human blood. Br J Clin Pharmacol 1992; 33: 319-22
119. Lipsky JJ. Zalcitabine and didanosine. Lancet 1993; 341: 30-2
120. 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: 1166-71
121. Cato A, Qian J, Caruthers L, et al. Evaluation of the pharmacokinetic interaction between ritonavir and didanosine [abstract PI 59]. Clin Pharmacol Ther 1996; 59: 144
122. Barry M, Wild M, Veal G, et al. Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers. AIDS 1994; 8: F1-5
123. Veal GJ, Wild MJ, Barry MG, et al. Effects of dideoxyinosine and dideoxycytidine on the intracellular phosphorylation of zidovudine in human mononuclear cells. Br J Clin Pharmacol 1994; 38: 323-8
124. Veal GJ, Barry MG, Back DJ. Zalcitabine (ddC) phosphorylation and drug interactions. Antiviral Chem Chemother 1995; 6: 379-84