st.hosp.kyushu-u.ac.jp

A simple high-performance liquid chromatographic method was developed for the simultaneous determination of the therapeutic levels of acyclovir and ganciclovir in human plasma. After precipitation of plasma proteins with 6% perchloric acid, acyclovir and ganciclovir were simultaneously determined by reversed-phase chromatography with spectophotometric detection at 254 nm. The peak heights for acyclovir and ganciclovir were linearly related to their concentrations ranging from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and 99.26-103.07% for ganciclovir. The intra- and inter-day relative standard deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424% for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL determined as the signal-to-noise ratio of 3. The present method is applicable to therapeutic monitoring during antiviral medication. Copyright 2003 John Wiley & Sons, Ltd.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14648605&dopt=Abstract acyclovir Zovirax[PubMed - in process]




Arch Ophthalmol. 2003 Dec;121(12):1702-4.
Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection.

Uchoa UB, Rezende RA, Carrasco MA, Rapuano CJ, Laibson PR, Cohen EJ.

Cornea Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

OBJECTIVE: To evaluate the effectiveness of more than 12 months of oral acyclovir therapy in reducing recurrences of ocular herpes simplex virus. METHODS: We retrospectively compared ocular herpes simplex virus recurrence in 2 groups of patients. In group 1, patients used oral acyclovir for at least 12 months and then discontinued the treatment. In group 2, patients received the treatment for at least 18 months. We compared recurrences when both groups were using acyclovir (period 1) and when only group 2 was receiving the drug (period 2). Statistical analysis was performed with the t test, chi2 test, and Kaplan-Meier method. RESULTS: Group 1 had 18 patients and a mean +/- SD follow-up of 45.2 +/- 22.2 months. Group 2 had 22 patients and a mean +/- SD follow-up of 42.4 +/- 30.2 months. Six patients (33%) in group 1 and 4 patients (18%) in group 2 had recurrence in period 1 (P =.3). In period 2, 14 patients (78%) in group 1 and 8 patients (36%) in group 2 had recurrence (P =.01). Mean +/- SD recurrence-free survival in period 2 was 15.3 +/- 5.5 months in group 1 and 37.3 +/- 6.3 months in group 2 (P =.001). CONCLUSIONS: Long-term oral acyclovir use seems to remain effective in decreasing the number of ocular herpes simplex virus recurrences beyond 12 months.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14662588&dopt=Abstract acyclovir Zovirax




Contact Dermatitis. 2003 Sep;49(3):155-7.
Systemic acyclovir reaction subsequent to acyclovir contact allergy: which systemic antiviral drug should then be used?

Vernassiere C, Barbaud A, Trechot PH, Weber-Muller F, Schmutz JL.

Dermatology Department, Fournier Hospital, Nancy, France.

Allergic contact dermatitis caused by acyclovir is rare. We report the 5th case of systemic acyclovir reaction subsequent to acyclovir contact dermatitis, with investigations made to determine an alternative antiviral treatment. A 23-year-old woman, after dermatitis while using Zovirax cream, went on to develop urticaria after oral acyclovir. Patch tests were performed with the components of Zovirax cream (acyclovir, propylene glycol and sodium lauryl sulfate) and with other antiviral drugs. Patch tests were positive to Zovirax cream, acyclovir, valacyclovir and propylene glycol. Patch and prick tests with famciclovir were negative, but its oral administration caused an itchy erythematous dermatitis on the trunk and extremities. Our patient developed a systemic acyclovir reaction subsequent to acyclovir allergic contact dermatitis, with cross-reactions to valacyclovir and famciclovir. Their common chemical structure is the 2-aminopurine nucleus. It is probably this part of the molecule that provokes both contact allergy and systemic reactions. The only antiviral drugs not having this core are foscarnet and cidofovir, and these could therefore be alternatives.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14678212&dopt=Abstract acyclovir Zovirax[PubMed - in process]




Pharm Res. 1998 Aug;15(8):1154-9.
5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter.

Han H, de Vrueh RL, Rhie JK, Covitz KM, Smith PL, Lee CP, Oh DM, Sadee W, Amidon GL.

College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.

PURPOSE: General use of nucleoside analogues in the treatment of viral infections and cancer is often limited by poor oral absorption. Valacyclovir, a water soluble amino acid ester prodrug of acyclovir has been reported to increase the oral bioavailability of acyclovir but its absorption mechanism is unknown. This study characterized the intestinal absorption mechanism of 5' -amino acid ester prodrugs of the antiviral drugs and examined the potential of amino acid esters as an effective strategy for improving oral drug absorption. METHODS: Acyclovir (ACV) and Zidovudine (AZT) were selected as the different sugar-modified nucleoside antiviral agents and synthesized to L-valyl esters of ACV and AZT (L-Val-ACV and L-Val-AZT), D-valyl ester of ACV (D-Val-ACV) and glycly ester of ACV (Gly-ACV). The intestinal absorption mechanism of these 5' -amino acid ester prodrugs was characterized in three different experimental systems; in situ rat perfusion model, CHO/hPEPT1 cells and Caco-2 cells. RESULTS: Testing 5' -amino acid ester prodrugs of acyclovir and AZT, we found that the prodrugs increased the intestinal permeability of the parent nucleoside analogue 3- to 10-fold. The dose- dependent permeation enhancement was selective for L-amino acid esters. Competitive inhibition studies in rats and in CHO cells transfected with the human peptide transporter, hPEPT1, demonstrated that membrane transport of the prodrugs was mediated predominantly by the PEPT1 H+/dipeptide cotransporter even though these prodrugs did not possess a peptide bond. Finally, transport studies in Caco-2 cells confirmed that the 5' - amino acid ester prodrugs enhanced the transcellular transport of the parent drug. CONCLUSIONS: This study demonstrates that L-amino acid-nucleoside chimeras can serve as prodrugs to enhance intestinal absorption via the PEPT1 transporter, providing a novel strategy for improving oral therapy of nucleoside drugs.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9706043&dopt=Abstract acyclovir Zovirax

iupui.edu

Four types of therapeutic strategies for managing cytomegalovirus (CMV) in solid organ transplant recipients, the mechanisms of action and efficacy of drugs used for prophylaxis, and the criteria for evaluating drugs for inclusion in a formulary are described. Universal and selective prophylaxis are simple to implement and effective for CMV prophylaxis, but they are costly and patient nonadherence and viral resistance can develop. Preemptive therapy may cause less resistance and cost less, but it is more complex and associated with a higher incidence of infection, which may have no effect on secondary effects from CMV infection, and higher recurrence of disease than prophylactic therapy. Treatment of active disease may be less costly for the drug than other approaches, but intravenous access is required and the rates of infection recurrence and mortality are higher compared with prophylaxis and preemptive therapy. Criteria for deciding which CMV prophylactic drugs to include in a formulary include efficacy, safety, convenience, and cost. CMV immune globulin i.v. is costly and exhibits reduced efficacy when used alone in patients at high risk for CMV disease. Intravenous ganciclovir is effective, but it is costly because of infusion costs. Intravenous drug therapies are inconvenient and associated with a risk of bacterial and fungal infection. Oral acyclovir is safe to use and inexpensive (since a genetic exists), but it has poor efficacy and is inconvenient because of the need for four large daily doses. Valacyclovir is more convenient and with similar safety and probably better efficacy than acyclovir, but it is more costly. Oral ganciclovir and oral valganciclovir have similar safety and costs, with greater efficacy than acyclovir. The single daily dose and lack of resistance to valganciclovir are advantages over oral ganciclovir, which requires three daily doses and can result in the development of resistance.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14686231&dopt=Abstract acyclovir Zovirax[PubMed - in process]