Pharm Res. 1998 Aug;15(8):1182-8.
Transbuccal delivery of acyclovir: I. In vitro determination of routes of buccal transport.

Shojaei AH, Berner B, Xiaoling L.

Department of Pharmaceutics and Medicinal Chemistry, School of Pharmacy, University of the Pacific, Stockton, California 95211, USA.

PURPOSE: To determine the major routes of buccal transport of acyclovir and to examine the effects of pH and permeation enhancer on drug permeation. METHODS: Permeation of acyclovir across porcine buccal mucosa was studied by using side-by-side through diffusion cells at 37 degrees C. The permeability of acyclovir was determined at pH range of 3.3 to 8.8. Permeability of different ionic species was calculated by fitting the permeation of data to a mathematical model. Acyclovir was quantified using HPLC. RESULTS: Higher steady state fluxes were observed at pH 3.3 and 8.8. The partition coefficient (1-octanol/buffer) and the solubility of acyclovir showed the same pH dependent profile as that of drug permeation. In the presence of sodium glycocholate (NaGC) (2-100 mM), the permeability of acyclovir across buccal mucosa was increased 2 to 9 times. This enhancement was independent of pH and reached a plateau above the critical micelle concentration of NaGC. The permeabilities of anionic, cationic, and zwitterionic species were 3.83 X 10-5, 4.33 X 10-5, and 6.24 x 10-6 cm/sec, respectively. CONCLUSIONS: The in vitro permeability of acyclovir across porcine buccal mucosa and the octanol-water partitioning of the drug were pH dependent. A model of the paracellular permeation of the anionic, cationic, and zwitterionic forms of acyclovir is consistent with these data. The paracellular route was the primary route of buccal transport of acyclovir, and the enhancement of transbuccal transport of acyclovir by sodium glycocholate (NaGC) appeared to operate via this paracellular route.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9706047&dopt=Abstract acyclovir Zovirax




Bone Marrow Transplant. 1996 May;17(5):813-7.
European survey of herpesvirus resistance to antiviral drugs in bone marrow transplant recipients. Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Reusser P, Cordonnier C, Einsele H, Engelhard D, Link D, Locasciulli A, Ljungman P.

Department of Medicine, University Hospital, Basel, Switzerland.

A survey of herpesvirus resistance to antiviral drugs was conducted by mailing a questionnaire to the centers of the European Group for Blood and Marrow Transplantation (EBMT). Results from 68 centers were reported. The number of centers with proven or suspected resistance of herpes simplex virus (HSV) was 17 (25%), of varicella-zoster virus (VZV) was three (4%), and of cytomegalovirus (CMV) was 19 (28%). Acyclovir-resistant HSV strains were recovered from 10 patients with HSV disease. Replacement of acyclovir by foscarnet in seven of these patients resulted in improved or healed HSV disease in five (17%). Acyclovir-resistant VZV was isolated from one patient with zoster which improved after a change to vidarabine therapy. CMV resistance to ganciclovir was proven in only two patients but was suspected in 23. Ganciclovir was replaced by foscarnet in 15 of these 25 patients which resulted in better virological and/or clinical outcome in 13 (87%). These results suggest that herpesvirus resistance is an emerging problem in marrow transplant recipients, and that foscarnet treatment may prove to be a valuable alternative when the presence of acyclovir- or ganciclovir-resistant herpesvirus disease is documented in these patients.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8733703&dopt=Abstract acyclovir Zovirax




Plast Reconstr Surg. 1996 Sep;98(3):427-33; discussion 434-5.
Prevention of facial herpetic infections after chemical peel and dermabrasion: new treatment strategies in the prophylaxis of patients undergoing procedures of the perioral area.

Perkins SW, Sklarew EC.

Indiana University Medical Center, Indianapolis, USA.

A proposed clinical strategy is offered for the prevention and treatment of facial herpetic infection associated with phenol chemical peel or dermabrasion of the perioral area. A retrospective evaluation of 181 consecutive patients undergoing perioral chemical peel or dermabrasion from 1983 to 1990 was performed. No patients were excluded and the minimum follow-up was 6 to 24 months. All procedures were done at a private practice ambulatory surgery center. Patients with any history of oral herpetic lesions were pretreated with oral acyclovir. The vast majority of these patients received dosages far exceeding previously described regiments. A subset of patients (n = 12) whose procedures predated acyclovir's commercial availability received no prophylactic treatment and allowed for a comparison group. The incidence of postoperative infection was measured to determine the effectiveness of prophylactic acyclovir treatment. In patients reporting previous herpetic infection, postoperative herpetic outbreaks were far more likely to occur (50 percent infection rate) in the absence of prophylactic acyclovir. An 8.3 percent infection rate was noted in patients with a similar history who received standard acyclovir prophylaxis. Once high dose prophylactic treatment was initiated, no further herpetic outbreaks were observed. Even among patients with a negative history of oral herpes (no treatment), 6.6 percent developed postoperative infections. Pretreatment with high dose acyclovir clinically minimizes the incidence and severity of postoperative herpetic infection in patients undergoing perioral chemical peel or dermabrasion. All patients should be treated preoperatively with acyclovir regardless of past history, because even those patients reporting no previous outbreaks of oral herpes may develop postoperative infections.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8700976&dopt=Abstract acyclovir Zovirax




Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3525-9.
Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy.

Black ME, Newcomb TG, Wilson HM, Loeb LA.

Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, School of Medicine, University of Washington, Seattle, 98195-7705, USA.

Herpes simplex virus type 1 (HSV-1) thymidine kinase is currently used as a suicide agent in the gene therapy of cancer. This therapy is based on the preferential phosphorylation of nucleoside analogs by tumor cells expressing HSV-1 thymidine kinase. However, the use of HSV-1 thymidine kinase is limited in part by the toxicity of the nucleoside analogs. We have used random sequence mutagenesis to create new HSV-1 thymidine kinases that, compared with wild-type thymidine kinase, render cells much more sensitive to specific nucleoside analogs. A segment of the HSV-1 thymidine kinase gene at the putative nucleoside binding site was substituted with random nucleotide sequences. Mutant enzymes that demonstrate preferential phosphorylation of the nucleoside analogs, ganciclovir or acyclovir, were selected from more than one million Escherichia coli transformants. Among the 426 active mutants we have isolated, 26 demonstrated enhanced sensitivity to ganciclovir, and 54 were more sensitive to acyclovir. Only 6 mutant enzymes displayed sensitivity to both ganciclovir and acyclovir when expressed in E. coli. Analysis of 3 drug-sensitive enzymes demonstrated that 1 produced stable mammalian cell transfectants that are 43-fold more sensitive to ganciclovir and 20-fold more sensitive to acyclovir.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8622970&dopt=Abstract acyclovir Zovirax




J Chromatogr B Biomed Sci Appl. 2000 Mar 10;739(2):231-7.
Rapid, simple and sensitive high-performance liquid chromatographic method for detection and determination of acyclovir in human plasma and its use in bioavailability studies.

Bangaru RA, Bansal YK, Rao AR, Gandhi TP.

Research and Development Unit, Cadila Pharmaceuticals Ltd., Ahemedabad, India.

A rapid, simple and sensitive reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the measurement of acyclovir concentrations in human plasma and its use in bioavailability studies is evaluated. Unchanged acyclovir has been quantified without the introduction of an internal standard using the present method. Human plasma proteins were selectively precipitated by the addition of 7% perchloric acid to spiked plasma samples or to the plasma samples obtained after acyclovir administration to human volunteers and the mixture was spun at 1000 g for 10 min. The supernatant was directly injected into a Novaflex C18 column and detected at 254 nm. The mobile phase consisted of octane sulfonic acid buffer (pH 2.5) and methanol (92:08). The limit of quantitation for acyclovir in plasma was 20 ng/ml, which enabled the determination of the area under the curve (AUC) more precisely, that is, it is much closer to its extrapolated value. The present method has been successfully applied to samples from bioavailability studies.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10755367&dopt=Abstract acyclovir Zovirax