Antimicrob Agents Chemother. 2002 Jun;46(6):1831-6.
Acyclovir, ganciclovir, and zidovudine transfer into rat milk.

Alcorn J, McNamara PJ.

Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.

Treatment with antiviral agents that accumulate in breast milk may offer a novel approach to reduce the rates of vertical transmission of important viruses and the risk of clinical illness in suckling neonates. The present study evaluated the extent and mechanism of transfer of three antiviral nucleoside analogues into milk in a lactating rat model system. Acyclovir (0.26 mg/h), ganciclovir (0.13 mg/h), and zidovudine (0.5 mg/h) were each infused to steady-state concentrations in six rats 15 to 16 days postpartum. The observed ratios of the concentrations in milk to the concentrations in serum (observed milk-to-serum ratio), calculated from the ratio of the steady-state concentration in serum to the steady-state concentration in milk, determined the extent of drug transfer into milk. To identify the mechanism of transfer into milk, the observed milk-to-serum ratio was compared to a predicted milk-to-serum ratio estimated from an in vitro passive diffusion model of transfer of each drug into milk. High-pressure liquid chromatography methods determined milk and serum drug concentrations. Mean +/- standard deviation observed milk-to-serum ratios for acyclovir, ganciclovir, and zidovudine were 5.1 +/- 1.4, 1.6 +/- 0.33, and 1.0 +/- 0.29, respectively, compared with their corresponding predicted ratios of 1.1, 0.85, and 0.71. These results suggest that acyclovir accumulates in milk due to active transport mechanisms, while passive diffusion processes govern the transfer of both ganciclovir and zidovudine into milk. The presence of all three antiviral drugs in milk and the potential for active drug transfer into milk warrants further investigation of the accumulation of other antiviral drugs in milk and their therapeutic benefits in reducing the vertical transmission of viruses and clinical sequelae in the breast-feeding infant.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12019097&dopt=Abstract acyclovir Zovirax




Pol J Pharmacol. 2002 Jan-Feb;54(1):45-53.
In vitro cytostatic activity of 8-substituted and tricyclic analogues of acyclovir.

Hladon B, Goslinski T, Laskowska H, Baranowski D, Ostrowski T, Zeidler J, Ruszkowski P, Golankiewicz B.

Department of Pharmacology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.

Out of a series of twenty 8-substituted or/and 1,N-2-bridged (tricyclic) derivatives of acyclovir (a selective antiherpetic drug), known to be nontoxic to normal cells, seven compounds were found to exhibit moderate cytostatic activity in KB human tumor tissue culture system with ED50 activity values ranging from 0.052-0.094 x 10(-3) mole/l. The structure-activity relationship analysis indicated that the primary factors determining their cytotoxicity were: 1) bromine atom at the C-8 position of the bicyclic derivatives and 2) unsubstituted appended ring in the tricyclic derivatives. Combination of two structural elements carrying the cytotoxicity gave diverse effects, enhancement or decrease in activity depending on particular cases. Two compounds (of four selected), 8-bromoacyclovir and 1,N-2-etheno-acyclovir, having unsubstituted 9-[(2-hydroxyethoxy)methyl] chain, showed approximately 2-fold increase in their cytotoxicity against HeLa tumor cells in the presence of the induced microsomal generating system suggesting that their cytotoxicity depends on the drug metabolic transformation into their active metabolites (intermediates) via MFO-system, and that structural unit of this chain is essential for abovementioned activation. Presently found remarkable cytotoxic selectivity of acyclovir analogues against KB and HeLa tumor cells together with previously reported in the literature specific cytotoxic activity of acyclovir against murine leukemia L 1210 cells seem to be encouraging for further investigation of this class of compounds in other tumor systems.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12020043&dopt=Abstract acyclovir Zovirax

otenet.gr

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections. Copyright 2002 S. Karger AG, Basel

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12021536&dopt=Abstract acyclovir Zovirax




Am J Health Syst Pharm. 1999 Sep 15;56(18):1831-4.
Comparison of ganciclovir- and immune globulin-containing regimens in preventing cytomegalovirus infection in patients with renal transplants.

Walton T, Sankari B, Wyner L.

Department of Pharmacy and Drug Information, Grady Health System, Atlanta, GA 30335-3801, USA.

The effectiveness and costs of ganciclovir compared with intravenous immune globulin (IVIG) in the prevention of cytomegalovirus (CMV) disease were studied. A retrospective analysis was conducted of renal transplant patients treated with ganciclovir during the initial hospital stay followed by three months of acyclovir therapy and a historical control group that received IVIG at one, two, four, six, and eight weeks posttransplant and acyclovir at two weeks posttransplant and continued for three months. The average drug cost for each regimen and the average direct cost of treating CMV disease in each group were calculated. The overall frequency of CMV disease was 14% in the IVIG group (n = 42) and 3% in the ganciclovir group (n = 30). CMV disease occurred less frequently in all ganciclovir-treated subgroups, but the difference was significant only in the group in which the recipient was CMV seronegative and the donor CMV seropositive. No ganciclovir-related adverse events were noted. Three IVIG-related infusion reactions were noted. Treatment with ganciclovir decreased drug costs by approximately $2,775 per patient or $83,250 for the study sample. The overall avoided cost in the ganciclovir group was $102,575 ($3,419 per patient). Ganciclovir followed by acyclovir was significantly more effective than IVIG followed by acyclovir in the prevention of CMV disease in CMV-seronegative patients who received renal transplants from CMV-seropositive donors; among all patients studied, ganciclovir did not differ from IVIG in preventing CMV infection but was considerably less expensive.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10511232&dopt=Abstract acyclovir Zovirax

leo-pharma.com

L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepT1) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity of L-valacyclovir for PepT1 is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions of L-valacyclovir with PepT1, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepT1 in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepT1 in binding studies, but only the purine analog (as the L-valine ester) showed PepT1-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepT1.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12113886&dopt=Abstract acyclovir Zovirax