Nephron. 1995;69(4):428-32.
Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis.

Almond MK, Fan S, Dhillon S, Pollock AM, Raftery MJ.

Department of Nephrology, Royal London Hospital, London, UK.

Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 +/- 1.76 microM, range 8.5-17.5 microM) with the half-life calculated to be 20.2 +/- 4.6 h. Mean plasma level of 6.29 +/- 0.94 microM were within the quoted range to inhibit herpes zoster virus (4-8 microM) at 18 h. Haemodialysis (4-5 h) eliminated 51 +/- 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 +/- 0.8 microM. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 +/- 1.0 microM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7777108&dopt=Abstract acyclovir Zovirax




Arch Dis Child. 1993 Dec;69(6):639-42; discussion 642-3.
Effect of oral acyclovir against primary and secondary viraemia in incubation period of varicella.

Suga S, Yoshikawa T, Ozaki T, Asano Y.

Department of Paediatrics, Toyokawa City Hospital, Japan.

The effect of oral acyclovir (approximately 40 mg/kg daily in four divided doses) against primary and secondary viraemia of varicella zoster virus (VZV) was examined in 27 children susceptible to VZV who were exposed to the virus in their families and their clinical features were compared with those of 19 non-treated subjects. The infection was confirmed by a fluorescent antibody to membrane antigen assay in 11 (85%) of 13 children who received acyclovir for the first seven days after exposure to VZV and in 11 (79%) of 14 who received acyclovir for the next seven days. The geometric mean antibody titre of the former group was significantly higher than that of the latter group. Varicella developed in 10 (91%) and was subclinical in one (9%) in the former group, whereas a very mild disease occurred in three (27%) and was subclinical in eight (73%) in the latter group. The severity of varicella was significantly greater in the former group than that in the latter group. On the other hand, all of the control group developed typical varicella and their clinical features were more severe than those of the acyclovir administered group. These data indicate that oral acyclovir more effectively inhibits replication of VZV in secondary viraemia than that of the primary viraemia.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8285774&dopt=Abstract acyclovir Zovirax




Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2000 Dec;14(4):379-81.
[An experimental study of a new route for Acyclovir administration for anti-keratitis therapeutic treatment]

Wang B, Teng W, Han X.

Department of Ophthalmology, Second Clinical Medical College, Harbin Medical University, Harbin 150086, China.

OBJECTIVE: To study the significance of a collagen shield made by centrifugal method that can deliver Acyclovir. METHODS: 28 white rabbits were divided into four groups for observing releasing of Acyclovir into aqueous at 0.5, 1, 3, 5 hours after adding drugs in two different administrative ways, that were putting drug loaded collagen shields on one eye of the rabbit and subconjunctival injection of drug in another eye of the rabbit as control. The drug concentrations in aqueous of rabbit at different times using different administrative routes were measured by high-performance liquid chromatography (HPLC). RESULTS: At 0.5 hr of drug administration, the Acyclovir concentrations in aqueous of subconjunctival injected rabbits were obviously higher than that in collagen shields loaded rabbits (t = 4.050, P <0.01), but it became not so notable at the time of 1 hr. (t =2.074, P>0.05). At the time of 3 hrs and 5 hrs, the drug concentrations in aqueous of collagen shield loaded eyes of the rabbits not only were higher than that of the subconjunctival injected rabbits (t=4.761, t=4.190, respectively, P <0.01), but also could sustain rather a long time. CONCLUSIONS: A drug delivering way using collagen shield made by centrifugal method can replace the subconjunctival injection.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11471033&dopt=Abstract acyclovir Zovirax




Am J Obstet Gynecol. 1994 Apr;170(4):967-72; discussion 972-3.
The transfer of the nucleoside analog ganciclovir across the perfused human placenta.

Gilstrap LC, Bawdon RE, Roberts SW, Sobhi S.

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032.

OBJECTIVE: The purpose of this study was to compare the maternal-fetal placental transfer of the antiviral nucleoside analog ganciclovir to that of acyclovir and to investigate the mechanism of transport. STUDY DESIGN: The ex vivo human placental cotyledon model was used. Carbon 14-labeled antipyrine was used as the reference compound to determine the clearance index of both antiviral agents. Dinitrobenzylthioinosine was used as a nucleoside transport inhibitor to help determine the transfer mechanism of each agent. RESULTS: The clearance index for ganciclovir was 0.17 +/- 0.08 and 0.20 +/- 0.10 at 1 and 10 micrograms/ml maternal concentrations. This was similar to the clearance index for acyclovir, which was 0.17 +/- 0.06 and 0.18 +/- 0.12, respectively. The clearance index for ganciclovir was not significantly affected by the addition of 5 mumol/L dinitrobenzylthionosine to the perfusate (0.25 +/- 0.09 vs 0.20 +/- 0.05). The same was true for acyclovir (0.29 +/- 0.06 vs 0.22 +/- 0.07). When the closed system and maternal ganciclovir concentrations of 1.0, 10.0, and 100 micrograms/ml were used, the percent fetal levels compared with maternal levels at 1 hour were 17.2%, 19.2%, and 17.3%, respectively. For acyclovir the fetal levels were 15.6%, 9.1%, and 8.9% compared with maternal levels. CONCLUSION: The antiviral agents ganciclovir and acyclovir appear to cross the placenta by simple diffusion, at least at therapeutic levels, and this transfer is not affected by the nucleoside transport inhibitor dinitrobenzylthioinosine.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8166217&dopt=Abstract acyclovir Zovirax




Schweiz Med Wochenschr. 1994 Jan 29;124(4):152-8.
[Resistance to virostatic agents in Herpes viruses: mechanism, incidence and clinical significance]

[Article in German]

Reusser P.

Departement fur Innere Medizin, Kantonsspital Basel.

Following the introduction of potent antiviral agents against herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV) into clinical use, the isolation of resistant virus strains has been reported with increasing frequency. The first part of this overview focuses on the mechanisms of action of acyclovir, ganciclovir, and forcarnet, and on the mechanisms of viral resistance. In the second part, the incidence and clinical importance of resistant herpes viruses are discussed. Among immunocompetent patients, herpes virus resistance is a rare event even in the case of long-term treatment with acyclovir for suppression of genital herpes. By contrast, among immunocompromised hosts, the isolation of resistant herpes virus strains from patients with disease unresponsive to antiviral drugs is not infrequent. The incidence of acyclovir-resistant HSV isolates in two large studies was 5%, and that of ganciclovir-resistant CMV strains was reported to be about 7%. At present, data on infections due to resistant VZV strains are scarce. Results from case reports and small series suggest some clinical benefit from the use of foscarnet when acyclovir-resistant HSV or VZV is present, or when CMV disease is caused by ganciclovir-resistant strains. Broader use of susceptibility testing to antiviral drugs and the development of new antiherpetic agents are required to improve the diagnosis and treatment of disease due to resistant herpes viruses.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8128197&dopt=Abstract acyclovir Zovirax