- Effect of Biphenyl Hydrolase-Like (BPHL) Gene Disruption on the Intestinal Stability, Permeability and Absorption of Valacyclovir in Wildtype and Bphl Knockout Mice. [Journal Article]
- BPBiochem Pharmacol 2018 Aug 16
- Biphenyl hydrolase-like protein (BPHL) is a novel human serine hydrolase that was originally cloned from a breast carcinoma cDNA library and shown to convert valacyclovir to acyclovir and valganciclo...
Biphenyl hydrolase-like protein (BPHL) is a novel human serine hydrolase that was originally cloned from a breast carcinoma cDNA library and shown to convert valacyclovir to acyclovir and valganciclovir to ganciclovir. However, the exclusivity of this process has not been determined and, indeed, it is possible that a number of esterases/proteases may mediate the hydrolysis of valacyclovir and similar prodrugs. The objectives of the present study were to evaluate the in situ intestinal permeability and stability of valacyclovir in wildtype (WT) and Bphl knockout (KO) mice, as well as the in vivo oral absorption and intravenous disposition of valacyclovir and acyclovir in the two mouse genotypes. We found that Bphl knockout mice had no obvious phenotype and that Bphl ablation did not alter the jejunal permeability of valacyclovir during in situ perfusions (i.e., 0.54 x10-4 in WT vs. 0.53 x10-4 cm/sec in KO). Whereas no meaningful changes occurred between genotypes in the gene expression of proton-coupled oligopeptide transporters (i.e., PepT1, PepT2, PhT1, PhT2), enzymatic upregulation of Cyp3a11, Cyp3a16, Abhd14a and Abhd14b was observed in some tissues of Bphl knockout mice. Most importantly, we found that valacyclovir was rapidly and efficiently hydrolyzed to acyclovir in the absence of BPHL, and that hydrolysis was more extensive after the oral vs. intravenous route of administration (for both genotypes). Taken as a whole, BPHL is not obligatory for the conversion of valacyclovir to acyclovir either presystemically or systemically.
- Efficacy of Brincidofovir as prophylaxis against HSV and VZV in hematopoietic cell transplant recipients. [Journal Article]
- TITranspl Infect Dis 2018 Aug 18; :e12977
- CONCLUSIONS: The overall rate of breakthrough HSV infection was 1.0 per 1,000 patient-days, without any breakthrough VZV infections. Our study provides the only available -albeit limited- evidence on the potential efficacy of BCV for HSV/VZV prophylaxis in HCT patients. Additional studies are needed to further assess the efficacy and safety of BCV in the setting. This article is protected by copyright. All rights reserved.
- The efficacy of oral acyclovir during early course of pityriasis rosea: a systematic review and meta-analysis. [Journal Article]
- JDJ Dermatolog Treat 2018 Aug 15; :1-25
- CONCLUSIONS: Oral acyclovir may be a relatively safe and effective treatment in early course of PR, and patients with PR may achieve faster symptoms control with acyclovir.
- Review for Disease of the Year: Treatment of Viral Anterior Uveitis: A Perspective. [Journal Article]
- OIOcul Immunol Inflamm 2018 Aug 10; :1-8
- CONCLUSIONS: Oral acyclovir, valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV-induced infections. Brivudin serves as an alternative in insufficiently responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to 12-month course of prophylactic treatment against recurrences is worth considering.
- Acute Viral Encephalitis. [Review]
- NEJMN Engl J Med 2018 Aug 09; 379(6):557-566
- Incidence and predictors of intravenous acyclovir-induced nephrotoxicity. [Journal Article]
- EJEur J Clin Microbiol Infect Dis 2018 Aug 07
- To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in No...
To assess the incidence, predictive factors, and prognosis of acyclovir-induced nephrotoxicity. We conducted a historical prospective cohort study of patients treated with intravenous acyclovir in North Denmark Region from 2009 to 2016. Information on baseline demographics, co-morbidities, plasma creatinine, and treatment was obtained from the medical records. The primary outcome was an increase of ≥ 40 μmol/L in plasma creatinine level from baseline. We included 276 patients treated with intravenous acyclovir of which 29 (10.5%) met the primary outcome. In 14 cases, the treating physician considered acyclovir the main reason for nephrotoxicity, whereas a potential competing cause of renal impairment was present among the 15 remaining patients. Hypertension was the only predictive factor associated with nephrotoxicity (risk ratio (RR), 2.77; 95% confidence interval (CI), 1.41-5.46), while having no co-morbidities was protective (RR, 0.32; CI, 0.16-0.63). In all cases, the nephrotoxicity was reversible following rehydration and dose reduction or discontinuation of the drug. However, the normalized plasma creatinine upon treatment was significantly higher between cases with acyclovir-induced nephrotoxicity than cases with a potential competing cause (median [interquartile range (IQR)], 93.5 μmol/L [85-108] vs 75 μmol/L [66.5-88]; p = 0.019). Acyclovir-induced, reversible nephrotoxicity was observed in 5.1-10.5% of patients. It is difficult to predict who will develop acyclovir-induced nephrotoxicity; it may occur late in treatment and hypertension was the only independent predictive factor, while the absence of co-morbidities was protective. Ensuring hydration, frequent evaluations of renal function, and corresponding dose adjustment of intravenous acyclovir treatment seem prudent.
- A physiologically based pharmacokinetic model for valacyclovir established based on absolute expression quantity of hPEPT1 and its application. [Journal Article]
- EJEur J Pharm Sci 2018 Aug 03
- In this study, a physiologically based pharmacokinetic (PBPK) model was established for valacyclovir based on absolute expression quantity of hPEPT1 along the entire length of the human intestine and...
In this study, a physiologically based pharmacokinetic (PBPK) model was established for valacyclovir based on absolute expression quantity of hPEPT1 along the entire length of the human intestine and other reliable in vitro, in vivo observed data. The PBPK model-3 defined acyclovir as metabolite of valacyclovir and simulated the plasma concentration-time profiles of valacyclovir and acyclovir simultaneously. It was validated strictly by a series of observed plasma concentration-time profiles. The average fold error (AFE) and absolute average fold error (AAFE) values were all smaller than 2. Then, it was used to quantitatively evaluate the effect of hPEPT1, luminal degradation rate, drug release rate and gastric residence time on the oral absorption of valacyclovir and acyclovir. The PBPK model-3 suggests that mainly 75% of valacyclovir was absorbed by active transport of hPEPT1. The luminal degradation of valacyclovir in the upper intestinal lumen cannot be considered the only reason for its incomplete bioavailability. The plasma concentration-time profiles of valacyclovir and its metabolite acyclovir were not sensitive to dissolution rate faster than T85% = 120 min. Prolonged gastric residence time of sustained release tablet can improve the oral absorption of valacyclovir. All in all, the PBPK model-3 in this study is reliable and accurate. It is useful for the research of clinical application and dosage forms design of valacyclovir.
- High incidence of early human Herpes Virus-6 infection in children undergoing haploidentical manipulated stem cell transplantation for haematological malignancies. [Journal Article]
- BBBiol Blood Marrow Transplant 2018 Jul 29
- CONCLUSIONS: All 38 pediatric patients undergoing these manipulated haploidentical HSCT showed HHV-6 reactivation and 14/38 developed HHV-6 disease with similar features in terms of timing, morbidity, response to treatment and outcome. The graft composition in both transplant platforms, rich in CD4+ T cells and poor in NK cells, seems to play a key role. HHV-6 DNAemia surveillance was useful to diagnose and treat pre-emptively HHV-6 infection.
- Improvement of refractory acyclovir-resistant herpes simplex virus type 1 infection by continuous acyclovir administration. [Journal Article]
- JIJ Infect Chemother 2018 Jul 28
- Resistant herpes simplex virus type 1 (HSV-1) infection is sometimes fatal for immunocompromised patients. Here, we report 10-year-old girl receiving hematopoietic stem cell transplantation developed...
Resistant herpes simplex virus type 1 (HSV-1) infection is sometimes fatal for immunocompromised patients. Here, we report 10-year-old girl receiving hematopoietic stem cell transplantation developed refractory HSV-1 infection, which was persisted to intermittent acyclovir (ACV) or foscarnet (FOS) administrations but was improved by continuous ACV administration. The isolates from the lesion were identified with low susceptibilities to ACV and FOS by plaque reduction assay due to DNA pol gene mutation. Continuous ACV administration overcomes the efficacy of intermittent administration and could be the best option to treat severe HSV-1 infectious patients.
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- Frey syndrome following herpes zoster in an otherwise healthy girl. [Journal Article]
- BCBMJ Case Rep 2018 Jul 25; 2018
- A 12-year-old girl presented with red spots appearing on the left side of her face. The girl was usually healthy and fully vaccinated, including varicella vaccination.Six years prior to her presentat...
A 12-year-old girl presented with red spots appearing on the left side of her face. The girl was usually healthy and fully vaccinated, including varicella vaccination.Six years prior to her presentation, she had suffered an episode of blister rash on the left side of her face, including lesions in the ear canal and buccal mucous membrane. A diagnosis of herpes zoster was made, and she was treated with acyclovir with complete skin recovery. A hearing examination demonstrated mild-to-moderate left neurosensory hearing loss.Since then, she is having short episodes of redness on her face without pain or sweating at the exact distribution of the zoster blisters 6 years ago. The appearance of spots is related to sour foods, such as sour flavoured candies, yoghourt and green apples. The diagnosis of postherpetic Frey syndrome was made, and observational approach was adopted due to the benign character of symptoms.