Obstet Gynecol. 1996 Oct;88(4 Pt 1):603-10.
Acyclovir prophylaxis in late pregnancy to prevent neonatal herpes: a cost-effectiveness analysis.

Randolph AG, Hartshorn RM, Washington AE.

Department of Pediatrics and Obstetrics, Institute for Health Policy Studies, School of Medicine, University of California, San Francisco, USA.

OBJECTIVE: To compare the cost-effectiveness of oral acyclovir prophylaxis in late pregnancy to the current strategy of cesarean delivery for genital herpes lesions in the prevention of neonatal herpes transmission from mothers with recurrent genital infections. METHODS: Decision analysis was used to evaluate the clinical outcomes and direct costs of a prevention program from the health care payer's perspective. Probabilities were obtained from the literature and experts. Cost data were based on hospital costs and a cohort of herpes-infected neonates. RESULTS: Acyclovir prophylaxis during late pregnancy followed by cesarean delivery for genital lesions at delivery in women with recurrent genital herpes requires 1818 women to follow this strategy to prevent one neonatal infection and 7.4 women to take acyclovir to prevent one outbreak of genital herpes at delivery, at a cost (above no intervention) of over $493,000 per neonatal infection prevented, $1.1 million per neonatal death or disability prevented, and $1444 per maternal outbreak prevented. Cesarean delivery for genital herpes lesions requires 386 women with recurrent herpes to undergo cesareans to prevent one neonatal infection, at a cost of more than $1.3 million per neonatal infection prevented and more than $3 million per neonatal death or disability prevented. If acyclovir is given and herpes lesions still occur, the incremental cost of requiring cesarean delivery for these women over vaginal delivery with culture and follow-up of exposed infants is more than $1.4 million per neonatal infection prevented. CONCLUSION: Oral acyclovir prophylaxis in late pregnancy for women with recurrent genital herpes is more cost-effective than the current strategy of cesarean delivery for all women presenting with genital herpes lesions.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8841227&dopt=Abstract acyclovir Zovirax




J Control Release. 2000 Jan 3;63(1-2):135-40.
Acyclovir-containing liposomes for potential ocular delivery. Corneal penetration and absorption.

Law SL, Huang KJ, Chiang CH.

Pharmaceutics Research Laboratory, Department of Medical Research, Veterans General Hospital-Taipei, Taipei, Taiwan.

The in vitro corneal penetration and in vivo corneal absorption of acyclovir from an acyclovir-containing liposome system were investigated. Results of in vitro corneal penetration demonstrated that positively charged liposomes resulted in a penetration rate lower than those of negatively charged liposomes and free acyclovir in solution. An in vivo study indicated that the extent of acyclovir absorption from positively charged liposomes was higher that those from negatively charged liposomes and free acyclovir. The acyclovir concentration in the cornea after administration of positively charged liposomes showed that an acyclovir deposition in the cornea was greater than those of negatively charged liposomes and free acyclovir. From morphological observation of the cornea surface treated with liposomes, it was suggested that positively charged liposomes formed a completely coated layer on the cornea surface. These liposomes would bind intimately on the cornea surface, leading to an increase of residence time. Therefore, positively charged liposomes resulted in an increase of acyclovir (ACV) absorption.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10640587&dopt=Abstract acyclovir Zovirax

jikei.ac.jp

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11771732&dopt=Abstract acyclovir Zovirax




Antivir Chem Chemother. 1999 Sep;10(5):251-7.
Acyclovir treatment of skin lesions results in immune deviation in mice infected cutaneously with herpes simplex virus.

Li Z, Sato H, Fukuda Y, Kurokawa M, Kageyama S, Kawana T, Shiraki K.

Department of Virology, Toyama Medical and Pharmaceutical University, Japan.

Clinical observations indicate that the antibody response to herpes simplex virus (HSV) in patients undergoing acyclovir treatment is reduced and, although the exact mechanism is not clear, some authors interpret it as immunosuppression. In order to clarify the mechanism, we cutaneously infected mice with HSV-1 and treated the resulting skin lesions with acyclovir. The immune response to infection and treatment in these mice was then analysed. Acyclovir treatment was given orally (20 mg/kg, three times daily), starting on day 0 (D0), 2 (D2) or 4 (D4) after infection and continuing until day 10. The serum antibody titre and the severity of skin lesions were significantly higher in the shortest treatment group (D4) than in the longer treatment groups (D0 and D2). In contrast, a skin test analysing delayed-type hypersensitivity (DTH) to HSV antigen showed that the D0 and D2 groups exhibited stronger DTH than the D4 group. Acyclovir treatment failed to cause a dissociation between DTH and antibody production in mice immunized with inactivated HSV antigen. However, acyclovir treatment in infected mice suppressed the development of skin lesions and resulted in a dissociation between DTH response and antibody production, indicating a typical immune deviation. This was supported by a change in the ratio of the isotype antibody IgG2a to IgG1. The treatment of skin lesions with acyclovir reduced the level of antibody response, as observed clinically. This indicates that the reduced antibody response in patients treated with acyclovir may be, at least in part, due to immune deviation and not immunosuppression.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10574180&dopt=Abstract acyclovir Zovirax




J Pharmacol Exp Ther. 1998 Sep;286(3):1166-70.
Transport of L-valine-acyclovir via the oligopeptide transporter in the human intestinal cell line, Caco-2.

de Vrueh RL, Smith PL, Lee CP.

Department of Drug Delivery, Pharmaceutical Technologies, Smithkline Beecham Pharmaceuticals, Collegeville, Pennsylvania, USA.

It has been reported that conjugating acyclovir, a potent antiviral with low oral bioavailability, to L-valine increases its urinary excretion in rats. However, it was also reported that this increase is not found for the D-valine ester, suggesting that a carrier-mediated mechanism is involved in its intestinal absorption. Therefore, mechanisms involved in the transepithelial transport of L-valine-acyclovir were investigated using the intestinal cell line, Caco-2, as a model system for the intestinal epithelium. Only the mucosal-to-serosal transport of acyclovir was increased by conjugation with L-valine (approximately 7-fold), suggesting the involvement of a carrier-mediated mechanism. This conclusion was supported by the finding that this increase was saturable. The mucosal-to-serosal transport of L-valine-acyclovir could be inhibited by L-glycylsarcosine, but not by L-valine, suggesting the involvement of the dipeptide carrier. Also it was found that L-valine-acyclovir inhibits the uptake of cephalexin, a substrate for the oligopeptide transporter. Stability of the esters in either the mucosal or serosal bathing solution is more than 90% after completion of the transport study. However, after transport, the receiver solution contained approximately 90% of acyclovir. Based on these findings it was concluded that absorption of the L-valine ester of acyclovir occurs as a result of uptake by the oligopeptide transporter at the apical cell membrane followed by intracellular hydrolysis of the ester and efflux of acyclovir.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9732374&dopt=Abstract acyclovir Zovirax