Biol Pharm Bull. 1994 Aug;17(8):1141-3.
Skin penetration enhancement of acyclovir by prodrug-enhancer combination.

Bando H, Yamashita F, Takakura Y, Hashida M.

Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

The effectiveness of prodrug-enhancer combination in skin penetration enhancement was studied using acyclovir and its lipophilic prodrug, acyclovir butyrate, with octanol/water partition coefficient of 0.0123 and 0.402, respectively. In the in vitro diffusion experiment with rat skin, the total amount of acyclovir appearing in the receptor phase after administration of the aqueous suspension of acyclovir butyrate was smaller than that obtained after administration of acyclovir, but their permeability coefficients were almost equal. An enhancer, 1-geranylazacycloheptan-2-one (GACH) did not show a large penetration enhancement of acyclovir (3.37-fold) but demonstrated extensive enhancement effect on the prodrug (12.3-fold). Most of the prodrug appeared in the form of acyclovir in the receptor phase without GACH, but the appearance ratio of acyclovir to total flux decreased with an increase in pretreatment doses of GACH.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7820127&dopt=Abstract acyclovir Zovirax




Antimicrob Agents Chemother. 1994 Jun;38(6):1246-50.
Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility result for isolates of herpes simplex virus from human immunodeficiency virus-infected patients.

Safrin S, Elbeik T, Phan L, Robinson D, Rush J, Elbaggari A, Mills J.

Department of Medicine, University of California, San Francisco 94143.

In vitro susceptibility testing of herpes simplex virus (HSV) isolates will play an increasingly important role in guiding the clinical management of immunocompromised hosts who have lesions that are poorly responsive to therapy with standard antiviral agents. We assessed the correlation between the in vitro susceptibility result using a plaque reduction assay in Vero cells and the response to antiviral therapy with acyclovir or foscarnet for 243 clinical isolates of HSV collected from 115 human immunodeficiency virus-infected patients. The in vitro results and clinical responses were highly associated for both acyclovir and foscarnet (P < 0.001 and P < 0.001, respectively). The predictive values of a susceptible result (50% effective concentrations, < 2 micrograms/ml for acyclovir and < 100 micrograms/ml for foscarnet) for complete healing of lesions were 62% for acyclovir and 82% for foscarnet; the predictive values of a resistant result for failure to heal were 95% for acyclovir and 88% for foscarnet. Thus, in vitro testing has clinical utility in guiding therapy, although the 1 to 2 weeks required to derive a definitive result by the plaque reduction assay is a major limitation.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8092821&dopt=Abstract acyclovir Zovirax




Drug Metab Dispos. 1994 Jan-Feb;22(1):60-4.
Metabolic disposition of the acyclovir prodrug valaciclovir in the rat.

Burnette TC, de Miranda P.

Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, NC 27709.

The prodrug valaciclovir demonstrated good oral absorption, rapid distribution and elimination, and extensive biotransformation to acyclovir in male CD rats. The mean urinary excretion of radioactivity following oral and intravenous administration of [8-14C]valaciclovir (25 mg/kg) was 65% and 95% of the dose, respectively. Acyclovir was the predominant radiolabeled urinary metabolite accounting for 57% and 65% of the dose, respectively, with valaciclovir accounting for 2% and 23% of the dose, respectively. Radioactivity from an oral dose of [8-14C]valaciclovir (10 mg/kg) was distributed to all 14 tissues examined 20 min postdose. The stomach, small intestine, kidney, liver, lymph nodes, and skin received the highest exposure to radioactivity, and the brain received the lowest exposure. Radioactivity in most tissues cleared by 24 hr postdose, and that in urine and feces accounted for essentially all of the administered dose by 48 hr postdose. Acyclovir derived from valaciclovir (10 and 25 mg/kg) exhibited dose-independent pharmacokinetics. The Cmax and AUC for acyclovir achieved with orally administered valaciclovir were 8- and 4-fold higher, respectively, than those estimated for an equivalent dose of acyclovir. The half-life of acyclovir derived from valaciclovir was approximately 1 hr, whereas that of valaciclovir was approximately 7 min. Valaciclovir was more efficiently metabolized when administered orally, indicating first-pass intestinal and/or hepatic metabolism. Rapid hydrolysis of valaciclovir in rat liver and intestinal homogenates further suggested the significance of presystemic metabolism. These studies indicate that valaciclovir is an efficient acyclovir prodrug particularly suited for oral administration.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8149891&dopt=Abstract acyclovir Zovirax




AIDS. 1993 Oct;7(10):1337-43.
Epstein-Barr virus infection of HIV-seropositive individuals is transiently suppressed by high-dose acyclovir treatment.

Luxton JC, Williams I, Weller I, Crawford DH.

Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, UK.

OBJECTIVE: To assess whether oral acyclovir can eliminate persistent Epstein-Barr virus (EBV) infection and thereby prevent EBV-associated lymphoma development in HIV-seropositive homosexual men. METHOD: Persistent EBV infection was examined in a group of 21 HIV-seropositive homosexual men before, during and after treatment with oral acyclovir at a dose of 800 mg every 6 h (10 individuals) or with a placebo (11 individuals). RESULTS: In 13 individuals, EBV was isolated from the oropharynx before and after treatment (seven cases from the acyclovir-treated group and six from the placebo-treated group). A significant reduction in virus isolation occurred during treatment in the acyclovir-treated group, but not in the placebo-treated group. In seven cases in whom EBV shedding was detected before and after treatment, the EBV strain isolated was identical throughout the study, even when acyclovir had abolished detectable shedding for the duration of the treatment. In two other cases more than one strain was detected. On examination of the EBV type present, 89% of a group of 18 patients consistently shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection with both virus types. This compares with figures of 100, 0 and 0%, respectively, in a control group of HIV-seronegative individuals. CONCLUSIONS: High-dose acyclovir therapy does not eliminate persistent EBV infection from the oropharynx of healthy HIV-seropositive individuals and therefore would not necessarily prevent lymphoma development. Our results suggest that infection by type B EBV, and co-infections of both A and B type, are more common in HIV-seropositives than HIV-seronegatives.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8267906&dopt=Abstract acyclovir Zovirax




Obstet Gynecol. 1993 Jul;82(1):102-4.
Oral acyclovir and recurrent genital herpes during late pregnancy.

Haddad J, Langer B, Astruc D, Messer J, Lokiec F.

Service de Neonatologie, Hospital University of Strasbourg, France.

OBJECTIVE: To assess plasma acyclovir levels in pregnant women given oral acyclovir during late gestation and to determine the role and effect of oral acyclovir on asymptomatic shedding of virus in cases of recurrent genital herpes. METHODS: Five pregnant women with proven genital herpes isolate (herpes simplex virus [HSV] 2) after 37 weeks' gestation were studied. Oral acyclovir was administered every 8 hours at dosages of 300, 400, and 300 mg in two subjects, and 200 mg five times daily in the other three until delivery. Plasma acyclovir peak and trough levels were determined. Viral cultures were obtained from both the mothers and neonates at delivery. RESULTS: There was no difference in acyclovir plasma levels among the patients. Furthermore, acyclovir levels were comparable to those of nonpregnant adults. The drug failed to suppress asymptomatic shedding of virus and transmission of HSV 2 to the neonate in one of five of the patients. CONCLUSION: Our study suggests that asymptomatic shedding of virus is not prevented by use of oral acyclovir during late gestation in proven recurrent genital herpes even though plasma acyclovir levels were within the normal range.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8390630&dopt=Abstract acyclovir Zovirax