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ARTICLE |

Concurrent Zidovudine Levels in Semen and Serum Determined by Radioimmunoassay in Patients With AIDS or AIDS-Related Complex FREE

Keith Henry, MD; Barbara J. Chinnock; Richard P. Quinn, PhD; Courtney V. Fletcher, PharmD; Paulo de Miranda, PhD; Henry H. Balfour, Jr, MD
[+] Author Affiliations

Reprint requests to Box 437 UMHC, University of Minnesota, Harvard Street at E River Road, Minneapolis, MN 55455 (Dr Balfour).


JAMA. 1988;259(20):3023-3026. doi:10.1001/jama.1988.03720200045031
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Zidovudine was present in the semen and serum of six patients with acquired immunodeficiency syndrome or the related complex who were receiving 200 mg of the drug orally every four to six hours. Mean semen zidovudine levels (as measured by a new radioimmunoassay) in samples collected 0.75 to 1.25 hours after oral dosing were 3.63 to 7.19 μmol/L. Levels in semen samples collected 3.0 to 4.5 hours after oral dosing were 1.68 to 6.43 μmol/L. These values are above the in vitro minimum inhibitory concentration for the human immunodeficiency virus type 1 (HIV-1). Mean serum concentrations at the early and late times after oral dosing were 0.22 to 3.07 μmol/L and 0.10 to 1.42 μmol/L, respectively. Ratios of semen/serum zidovudine levels ranged from 1.3 to 20.4. It is possible that a pH-dependent trapping mechanism, which has been described in the prostate for other antibiotics, was responsible for the relatively high semen levels observed.

(JAMA 1988;259:3023-3026)

REFERENCES

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;;317:185-191.
Richman DD, Fischl MA, Grieco MH, et al:  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1987;;317:192-197.
Zagury D, Bernard J, Leibowitch J, et al:  HTLV-III in cells cultured from semen of two patients with AIDS. Science 1984;;226:449-451.
Ho DD, Schooley RT, Rota TR, et al:  HTLV-III in the semen and blood of a healthy homosexual man. Science 1984;;226:451-453.
Stewart GJ, Cunningham AL, Driscoll GL, et al:  Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor. Lancet 1985;;2:581-584.
Poiesz B, Ehrlich G, Moore JL:  Incidence of HTLV-III infection in the semen of AIDS and ARC patients, abstracted. Clin Res 1986;;34:529A.
Quinn RP, de Miranda P, Gerald L, et al:  A sensitive radioimmunoassay for the antiviral agent BW 248U [9-(2-hydroxyethoxymethyl) guanine]. Anal Biochem 1979;;98:319-328.
Good SS, Reynolds DJ: Simultaneous quantitation of the anti-HIV agent 3′-azido-3′-deoxythymidine and its glucuronide in human serum by highperformance liquid chromatography. Presented at the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, Oct 5,1987.
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.
Coffey DS:  The biochemistry and physiology of the prostate and seminal vesicles , in Walsh PC, Gittes RE, Perlmuter AD, et al (eds): Campbell's Urology , ed 5. Philadelphia, WB Saunders Co, 1986;, pp 233-274.
Zimmerman TP, Mahony WB, Prus KL:  3′-azido-3′-deoxythymidine: An unusual nucleoside analogue that permeates the membrane of human erythrocytes and lymphocytes by nonfacilitated diffusion. J Biol Chem 1987;;262:5748-5754.
Yarchoan R, Broder S:  Development of antiretroviral therapy for the acquired immunodeficiency syndrome and related disorders. N Engl J Med 1987;;316:557-564.
Chinnock B, Fletcher C, Rhame F, et al: Pharmacokinetics of oral azidothymidine (AZT) in five AIDS patients. Presented at the Third International Conference on AIDS, Washington, DC, June 2, 1987.
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.
Wagner JG: Fundamentals of Clinical Pharmacokinetics . Washington, DC, Drug Intelligence Publications, 1975;, pp 359-395.
Anderson DJ, Hill JA: CD4 (T4)  lymphocytes in semen of healthy heterosexual men: Implications for the transmission of AIDS. Fertil Steril 1987;;48:703-704.
Klecker RW, Collins JM, Yarchoan R, et al:  Plasma and cerebrospinal fluid pharmacokinetics of 3′-azido-3′-deoxthymidine: A novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther 1987;;41:407-412.
Fletcher C, Chinnock B, Vicary C, et al: Cerebrospinal fluid (CSF) penetration of acyclovir (ACV) in patients with herpesvirus infections. Presented at the 25th Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Oct 1,1985.

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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;;317:185-191.
Richman DD, Fischl MA, Grieco MH, et al:  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 1987;;317:192-197.
Zagury D, Bernard J, Leibowitch J, et al:  HTLV-III in cells cultured from semen of two patients with AIDS. Science 1984;;226:449-451.
Ho DD, Schooley RT, Rota TR, et al:  HTLV-III in the semen and blood of a healthy homosexual man. Science 1984;;226:451-453.
Stewart GJ, Cunningham AL, Driscoll GL, et al:  Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor. Lancet 1985;;2:581-584.
Poiesz B, Ehrlich G, Moore JL:  Incidence of HTLV-III infection in the semen of AIDS and ARC patients, abstracted. Clin Res 1986;;34:529A.
Quinn RP, de Miranda P, Gerald L, et al:  A sensitive radioimmunoassay for the antiviral agent BW 248U [9-(2-hydroxyethoxymethyl) guanine]. Anal Biochem 1979;;98:319-328.
Good SS, Reynolds DJ: Simultaneous quantitation of the anti-HIV agent 3′-azido-3′-deoxythymidine and its glucuronide in human serum by highperformance liquid chromatography. Presented at the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, Oct 5,1987.
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.
Coffey DS:  The biochemistry and physiology of the prostate and seminal vesicles , in Walsh PC, Gittes RE, Perlmuter AD, et al (eds): Campbell's Urology , ed 5. Philadelphia, WB Saunders Co, 1986;, pp 233-274.
Zimmerman TP, Mahony WB, Prus KL:  3′-azido-3′-deoxythymidine: An unusual nucleoside analogue that permeates the membrane of human erythrocytes and lymphocytes by nonfacilitated diffusion. J Biol Chem 1987;;262:5748-5754.
Yarchoan R, Broder S:  Development of antiretroviral therapy for the acquired immunodeficiency syndrome and related disorders. N Engl J Med 1987;;316:557-564.
Chinnock B, Fletcher C, Rhame F, et al: Pharmacokinetics of oral azidothymidine (AZT) in five AIDS patients. Presented at the Third International Conference on AIDS, Washington, DC, June 2, 1987.
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.
Wagner JG: Fundamentals of Clinical Pharmacokinetics . Washington, DC, Drug Intelligence Publications, 1975;, pp 359-395.
Anderson DJ, Hill JA: CD4 (T4)  lymphocytes in semen of healthy heterosexual men: Implications for the transmission of AIDS. Fertil Steril 1987;;48:703-704.
Klecker RW, Collins JM, Yarchoan R, et al:  Plasma and cerebrospinal fluid pharmacokinetics of 3′-azido-3′-deoxthymidine: A novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clin Pharmacol Ther 1987;;41:407-412.
Fletcher C, Chinnock B, Vicary C, et al: Cerebrospinal fluid (CSF) penetration of acyclovir (ACV) in patients with herpesvirus infections. Presented at the 25th Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, Oct 1,1985.
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