Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption.

OBJECTIVE: To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana). ANIMALS: 15 African elephants (6 males and 9 females) of various ages. METHODS: Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling. RESULTS: Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 µg·h/mL), maximum observed concentration (Cmax; 3.73 µg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 µg·h/mL; Cmax, 2.52 µg/mL; and absorption t1/2, 0.13 hours. CONCLUSIONS: Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration. CLINICAL RELEVANCE: African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

A Comparison Between Effects of Amenamevir and Famciclovir on Intensities of Acute Pain and the Incidence of Postherpetic Neuralgia in Adult Patients with Herpes Zoster.

Objective: Herpes zoster (HZ) is a common disease, whose most common complication is postherpetic neuralgia (PHN). We conducted this study to compare effects of amenamevir (AMNV) and famciclovir (FCV) on intensities of acute HZ pain and the incidence of PHN, which have not been compared yet. Methods: After approval by the Ethics Committee, we retrospectively investigated adult patients with HZ treated with AMNV or FCV at Juntendo University Hospital between October, 2018 and February, 2020. We compared, between 143 AMNV-treated and 131 FCV-treated patients, pain scores of acute HZ pain evaluated on an 11-point numerical rating scale (NRS) and the incidence of PHN with the Mann-Whitney U test and Pearson's chi-square test, respectively. The univariate logistic regression analysis was used to identify predictors of PHN. Results: Pain scores during the acute HZ period remained significantly lower in AMNV-treated patients than FCV-treated patients (p = 0.049, 0.011, and 0.016 for Day 3-4, Day 7, and Week 2-3, respectively), although the pain score at Day 0 before treatment didn't differ between them (p > 0.05). The incidence of PHN didn't differ between them (9.8% vs. 11.5%, p > 0.05). In the total cohort, the pain score at Week 2-3 was significantly associated with the development of PHN (r 2 = 0.180, p < 0.00001). Conclusions: Compared with FCV, AMNV was more effective in reducing acute HZ pain, possibly reflecting its unique mechanism of action. However, AMNV didn't reduce the incidence of PHN possibly due to the multifactorial etiology of PHN.

In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies / A atividade in vitro de seis drogas antivirais contra o alfaherpesvírus equino tipo 1 indica que o ganciclovir é uma droga promissora para estudos in vivo

ABSTRACT: Equid alphaherpesvirus type 1 (EHV-1) is distributed worldwide and is a major agent of abortion, respiratory and neurological disease in horses. No specific treatment is available for EHV-1 infection, yet the potential of antiviral therapy has been explored. In this study we investigated the in vitro activity of Acyclovir, Ganciclovir, Foscarnet, Famciclovir, Vidarabina and Cidofovir against EHV-1. For this, the MTT test was performed, in which all the tested drugs showed no toxicity up to 200μg/mL. Subsequently, different drug concentrations were submitted to viral plaque reduction assays in cell culture. The selectivity index (SI) of the compounds was determined using the cytotoxic concentration for 50% of cells (CC50), obtained by MTT, and effective drug concentration to inhibit by 50% the number of viral plaques (EC50). Ganciclovir (SI: 490; EC50: 1.9 μg/mL) was the most efficient and safest drug against EHV-1, followed by Cidofovir (SI: 150, EC50: 5.7μg/mL), Acyclovir (SI: 37.4, EC50: 22.2μg/mL), Famciclovir (SI: 25.1, EC50: 24.5μg/mL), Vidarabine (SI: 12.2, EC50: 40.9μg/mL) and Foscarnet (SI: 6.9, EC50: 49.5 μg/mL), respectively. These results indicated that Ganciclovir (followed by Cidofovir), is a promising candidate for use in in vivo experiments.

RESUMO: O alfaherpesvírus equino tipo 1 (EHV-1) está amplamente distribuído nos rebanhos equinos de todo o mundo e é um dos principais agentes causadores de abortos, doença respiratória e neurológica em equinos. Ainda não há tratamento específico para a infecção pelo EHV-1 em equinos, mas o potencial da terapia antiviral tem sido investigado. Neste trabalho, foi investigada a atividade anti-herpética in vitro dos fármacos Aciclovir, Ganciclovir, Foscanet, Famciclovir, Vidarabina e Cidofovir frente ao EHV-1. Para isso, foi realizado o teste de MTT, em que todas as drogas não apresentaram citotoxicidade até a dose de 200μg/mL. A seguir, diferentes concentrações dos fármacos foram submetidas ao teste de redução de placas virais em cultivo celular. O índice de seletividade (IS) dos compostos foi determinado usando a concentração citotóxica para 50% dos cultivos celulares (CC50), obtida pelo MTT, e pela concentração dos fármacos efetiva para inibir em 50% o número de placas virais (EC50). O Ganciclovir (IS: 490; EC50: 1,9μg/mL) foi o mais eficiente e seguro frente ao EHV-1, seguido pelo Cidofovir (IS: 150; EC50: 5,7 μg/mL), Aciclovir (IS: 37,4; EC50: 22,2μg/mL), Famciclovir (IS: 25,1; EC50: 24,5μg/mL), Vidarabina (IS: 12,2; EC50: 40,9μg/mL) e Foscarnet (IS: 6,9; EC50: 49,5μg/mL). Estes resultados indicam que o Ganciclovir constitui-se em um candidato para uso em experimentos in vivo.

Sordera súbita: estudio retrospectivo sobre 40 casos ingresados en nuestro hospital / Sudden deafness: a retrospective study of 40 cases admitted to our hospital

Introducción: La sordera brusca es una pérdida súbita de audición a nivel neuro-sensorial, por causas desconocidas, y con mal pronóstico funcional. Las causas son desconocidas, lo que genera múltiples hipótesis y discusiones sobre esta patología. Objetivo: Evaluar los factores asociados al pronóstico y determinar los aspectos terapéuticos que influyen en el pronóstico de estos pacientes. Material y método: Revisamos las historias clínicas de los pacientes diagnosticados de sordera brusca durante un período de estudio de 4 años, y calculamos las frecuencias de las diferentes variables consideradas como relevantes; realizamos análisis bivariante y una comparación de las distribuciones mediante test de ANOVA y un análisis multivariante con regresión logística y lineal múltiple. Resultados: Analizamos 40 casos. Consideramos factores como el oído afectado, antecedentes cardiovasculares, HTA, diabetes, dislipemia, tabaco, hemoglobina, hematocrito, las circunstancias temporales y geográficas, de las que ninguna de ellas resultaron significativas para la recuperación. Tras el análisis de otros factores, encontramos un predominio de casos en verano y otoño (90 por ciento) frente a invierno y primavera (10 por ciento). El uso del famciclovir estuvo asociado a mayor probabilidad de recuperación completa OR 21,164 [1,265-374,47]. Por el contrario, estuvieron ligados a una menor probabilidad de recuperación completa: el tratamiento con medicina hiperbárica OR 0,013 [0,001-0,433], la curva audiométrica descendente OR 0,164 [0,032-0,533], y la presencia de vértigo asociada a acúfenos OR 0,158 [0,08-1,015]. La aspirina mejoró la recuperación de decibelios media 24,3 db IC 95 por ciento [1,00-47,61]. Conclusiones: El estudio es una serie retrospectiva cuyo análisis multivariante muestra que el famciclovir y el AAS tienen un efecto estadísticamente beneficioso en el tratamiento de la sordera súbita...

Introduction: The sudden deafness is a sudden loss of hearing at the neuro-senso-rial, for unknown reasons, and bad functional prognosis. The cause is unknown, generating multiple hypotheses and discussions on this topic. Aim: To evaluate the factors associated with prognosis and determine therapeutic aspects that influence the prognosis of these patients. Matherial and method: We reviewed the medical records ofpatients diagnosed with sudden hearing loss during a study period of 4 years, and calculate the frequencies of the different variables considered relevant; performed bivariate analysis and a comparison of the distributions byANOVA and a multivariate analysis with logistic regression and multiple lineal. Results: We analyzed 40 cases. We consider factors like the affected ear, cardiovascular history, hypertension, diabetes, dyslipidemia, snuff, hemoglobin, hematocrit, temporal and geographical, of which none were significant for recovery. After analysis of other factors, we found a predominance of cases in summer and autumn (90 percent) compared to winter and spring (10 percent). Use of famciclovir was associated with greater likelihood of complete recovery OR 21.164 [1.265 to 374.47]. On the contrary, were linked to a lower linked to a lower likelihood of full recovery: treatment with hyperbaric OR 0.013 [0.0010.0433] OR descending audiometric curve [0.164 0.032 to 0.533] and the presence of vertigo associated with tinnitus OR o.158 [0.08 to 1.015]. Aspirin improved recovery of 24.3 db decibel half 95 percent CI [1.00 to 47.61]. Conclusions: The study is a retrospective multivariate analysis which shows that famciclovir and aspirin have a statisfically beneficial in the treatment of sudden deafness, which in our sample is more frequent in summer and autumn. Biased studies are needed on these results may provide new hypotheses for treatment.