A Double-Blind, Placebo-Controlled Trial of the Effect of Chronically Administered Oral Acyclovir on Sperm Production in Men With Frequently Recurrent Genital Herpes

Douglas, John M.; Davis, Gray; Remington, Michael; Paulsen, C. Alvin; Perrin, Edward B.; Goodman, Phyllis J.; Conner, James D.; King, Dannie H.; Corey, Lawrence

doi:10.1093/infdis/157.3.588

Cited by 30 publications

(6 citation statements)

References 10 publications

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“…Current treatments include the nucleoside analogs acyclovir, famciclovir and valaciclovir (Vere Hodge & Field 2013). Acyclovir has been detected in semen, indicating that this nucleoside analog is capable of entering the MGT (Douglas Jr et al 1988). All of these studies strongly support the notion that the MGT is a sanctuary site that is capable of viral replication independent from the blood.…”

Section: Virus Transmission and Antiviral Therapy By Transepithelial supporting

confidence: 62%

Transepithelial transport across the blood–testis barrier

Miller

Cherrington

2018

Reproduction

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The blood–testis barrier protects developing germ cells by limiting the entry of xenobiotics into the adluminal compartment. There is strong evidence that the male genital tract can serve as a sanctuary site, an area of the body where tumors or viruses are able to survive treatments because most drugs are unable to reach therapeutic concentrations. Recent work has classified the expression and localization of endogenous transporters in the male genital tract as well as the discovery of a transepithelial transport pathway as the molecular mechanism by which nucleoside analogs may be able to circumvent the blood–testis barrier. Designing drug therapies that utilize transepithelial transport pathways may improve drug disposition to this sanctuary site. Strategies that improve disposition into the male genital tract could reduce the rate of testicular relapse, decrease viral load in semen, and improve therapeutic strategies for male fertility.

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Section: Virus Transmission and Antiviral Therapy By Transepithelial supporting

confidence: 62%

Transepithelial transport across the blood–testis barrier

Miller

Cherrington

2018

Reproduction

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“…Several mammalian membrane nucleoside transporters are able to concentrate nucleoside compounds against a concentration gradient. 28 Of interest, nucleoside analogs zidovudine, lamivudine, and acyclovir all appear to concentrate in semen relative to plasma, 21,29 whereas nonnucleoside analogs do not. 14,22 The finding of high seminal zidovudine-glucuronide concentrations also suggests active transport because this highly polar compound would not be expected to traverse membranes without facilitation.…”

Section: Discussionmentioning

confidence: 99%

Semen and Serum Pharmacokinetics of Zidovudine and Zidovudine‐Glucuronide in Men with HIV‐1 Infection

Anderson¹,

Noormohamed²,

Henry³

et al. 2000

Pharmacotherapy

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“…In male patients treated chronically with oral ACV as suppressive therapy, drug levels were consistently higher in semen than in plasma, with semen to plasma ratios of 1: 4 and 4: 2, after twice and five times daily dosing, respectively (Douglas et al, 1988).…”

Section: Humansmentioning

confidence: 94%

Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir

Good

Miranda

1992

Antivir Chem Chemother

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The acyclic nucleoside analogue, acyclovir, is an antiviral drug with activity against the herpes group of DNA viruses. Clinically, it is used as a selective therapeutic agent for the treatment of herpes simplex and varicella-zoster virus infections. Studies on the disposition of acyclovir, during the course of its preclinical and clinical development, indicated significant species differences in the absorption, metabolism and elimination of the drug. Gastrointestinal absorption was adequate in dogs and in mice; but in rats and primates it was limited to less than 20% of the administered dose. Whereas in some species (mice, rats, and dogs), acyclovir was virtually unmetabolized, significant biotransformation was apparent in guinea pigs, rabbits, and some primates. Acyclovir tissue distribution was extensive and indicated few differences across species. This review summarizes diverse studies on acyclovir absorption, metabolism, and disposition in different species, including humans, and indicates the relevance and importance of such studies in drug development.

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A Double-Blind, Placebo-Controlled Trial of the Effect of Chronically Administered Oral Acyclovir on Sperm Production in Men With Frequently Recurrent Genital Herpes

Cited by 30 publications

References 10 publications

Transepithelial transport across the blood–testis barrier

Transepithelial transport across the blood–testis barrier

Semen and Serum Pharmacokinetics of Zidovudine and Zidovudine‐Glucuronide in Men with HIV‐1 Infection

Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir

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