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

Henry, Keith; Chinnock, Barbara J.; Quinn, Richard P.; Fletcher, Courtney V.; Miranda, Paulo de; Balfour, Henry H.

doi:10.1001/jama.1988.03720200045031

Cited by 64 publications

(33 citation statements)

References 11 publications

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“…NRTIs ought not to penetrate the MGT because of lipid insolubility, yet NRTIs are the most penetrable ARV class, suggesting the involvement of drug sequestration or active transport (Reddy et al 2003;Taylor et al 2003a) (Table 2). Seminal zidovudine and lamivudine levels are twice that in blood (Henry et al 1988;Pereira et al 1999Pereira et al , 2000Reddy et al 2002). The observed seminal zidovudine level may result from drug binding to seminal protein (Anderson et al 2000).…”

Section: Nucleoside Reverse Transcriptase Inhibitors (Nrtis)mentioning

confidence: 92%

“…Despite a relatively low amount of drug being available systemically after first-pass metabolism (oral bioavailability 60%) (Bartlett & Gallant 2004), the drug concentration in semen is higher than that predicted by pharmacokinetics. Zidovudine may accumulate by ion trapping (Henry et al 1988). Ion trapping is based on the premise that ionization increases hydrophilicity, that is, only non-ionized drugs penetrate biological membranes (Taylor & Pereira 2001).…”

Section: Antiretroviral Drug Penetration Of Semenmentioning

confidence: 99%

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Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis

Chan

Ray

2007

Journal of Pharmacy and Pharmacology

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Antiretroviral therapy has reduced the morbidity and mortality associated with HIV-1/AIDS in developed countries. Viral replication in blood plasma is suppressed by antiretroviral drugs, whereas virus in the male genital tract is genetically and phenotypically unique and may not be suppressed. This viral compartmentalization affects antiretroviral drug penetration of the male genital tract and capacity for antiretroviral therapy to reduce sexual transmission. The problem of having two distinct viral populations within any given individual is compounded by the fact that antiretroviral drugs penetrate semen to varying degrees. Incomplete suppression of genital tract virus may yield drugresistant virus and increase the risk of sexual transmission. This review critically appraises current studies of antiretroviral drug quantification in semen and suggests recommendations to address observed limitations.

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Section: Nucleoside Reverse Transcriptase Inhibitors (Nrtis)mentioning

confidence: 92%

Section: Antiretroviral Drug Penetration Of Semenmentioning

confidence: 99%

Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis

Chan

Ray

2007

Journal of Pharmacy and Pharmacology

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“…Although zidovudine reaches high concentrations in semen (199), it does not appear to decrease shedding from this site (252), and this lack may have important implications for sexual transmission of disease.…”

Section: Zidovudinementioning

confidence: 98%

Antiviral therapy: current concepts and practices

Bean

1992

Clin Microbiol Rev

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Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.

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“…There is, however, significant hematologic toxicity associated with zidovudine, including anemia, neutropenia, pancytopenia, and bone marrow aplasia (3,5,16). The pharmacokinetics of zidovudine have been described previously (1,8,11,12,17). Although the relationship between levels in serum and toxicity or clinical outcome has not been defined, recent studies suggest that lower serum (and cerebrospinal fluid) zidovudine levels may increase the risk of HIV meningoencephalitis (7).…”

mentioning

confidence: 93%

Fluorescence polarization immunoassay for zidovudine

Granich

Eveland

Krogstad

1989

Antimicrob Agents Chemother

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We report a fluorescence polarization immunoassay (FPIA) for zidovudine (azidothymidine; Retrovir). This assay is accurate and specific over the clinically relevant range of zidovudine concentrations in serum (from 1 to 1,250 ng/ml; from 0.004 to 4.8 ,LM) and is unaffected by potentially interfering compounds in the sera of patients with renal or hepatic failure. Cross-reactivity with structural analogs of zidovudine (including zidovudine glucuronide) is less than 0.05%, except for cross-reactivities of 0.2, 0.3, and 0.4% with 3-methylthymidine, 3',5'-dideoxythymidine, and A22U (the optical isomer of zidovudine), respectively. The FPIA for zidovudine is more sensitive and more specific than high-performance liquid chromatography (HPLC); it requires 50 to 60 or 200 versus 500 ,il of serum and is faster to perform (45 specimens per h with the FPIA versus 3 specimens per h with HPLC). The zidovudine FPIA compares well with the radioimmunoassay. A correlation coefficient of 0.992 was observed with 31 serum specimens examined by both methods. All three assays (FPIA, radioimmunoassay, and HPLC) are unaffected by the heat treatment used to inactivate human immunodeficiency virus. The zidovudine FPIA should be particularly useful for analyzing specimens from large numbers of human immunodeficiency virus-infected patients receiving zidovudine in current clinical trials.

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

Cited by 64 publications

References 11 publications

Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis

Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis

Antiviral therapy: current concepts and practices

Fluorescence polarization immunoassay for zidovudine

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