Drugs online research references
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: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12019097&dopt=Abstract
Pediatr Infect Dis J. 1998 Oct;17(10):905-8.
Herpes zoster in children and adolescents.
Petursson G, Helgason S, Gudmundsson S, Sigurdsson JA.
Department of Family Medicine, University of Iceland, Reykjavik.
OBJECTIVES: To follow the clinical course of herpes zoster and to determine the incidence, frequency of complications and association with malignancy in children and adolescents. DESIGN: Prospective cohort study in a primary health care setting in Iceland. The main outcome measures were age and sex distribution of patients and discomfort or pain 1, 3 and 12 months after the rash and general health before and 3 to 6 years after the zoster episode. RESULTS: During observation of the target population for a period of 75750 person years, 121 episodes of acute zoster developed (incidence 1.6/1000/year) in 118 patients. End points were gained for all 118 patients after 554 person years of follow-up. Systemic acyclovir was never used. No patient developed postherpetic neuralgia, moderate or severe pain or any pain lasting longer than 1 month from start of the rash (95% confidence interval, 0 to 0.03). Potential immunomodulating conditions were diagnosed in 3 patients (2.5%) within 3 months of contracting zoster. Only 5 (4%) had a history of severe diseases. CONCLUSIONS: The probability of postherpetic neuralgia in children and adolescents is extremely low. Zoster is seldom associated with undiagnosed malignancy in the primary care setting.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9802633&dopt=Abstract
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: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12020043&dopt=Abstract
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