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Cureus Jan 2024Acyclovir is a widely used antiviral agent used to treat viral meningitis. Although well tolerated, on rare occasions, it can cause severe nephrotoxicity and...
Acyclovir is a widely used antiviral agent used to treat viral meningitis. Although well tolerated, on rare occasions, it can cause severe nephrotoxicity and neurotoxicity. It is recommended that the dose of intravenous acyclovir be calculated based on the ideal body weight for height rather than the actual weight in obese patients to avoid excessive dosage. We report two patients who developed severe acute kidney injury and neurological symptoms while on intravenous acyclovir therapy. The first patient was a 57-year-old obese woman known to have epilepsy who received a dose of intravenous acyclovir based on her actual weight of 80 kg and subsequently developed acyclovir-induced nephrotoxicity and increased seizure activity. The second patient was a 60-year-old, slightly overweight, man, who received a dose of intravenous acyclovir based on his actual weight of 80 kg and subsequently developed both acyclovir-induced nephrotoxicity and possible neurotoxicity. No other cause for the deterioration in renal function or neurological symptoms was identified, and there was rapid recovery within three days of stopping acyclovir therapy. This case report emphasizes the importance of monitoring renal function while patients are on intravenous acyclovir therapy and highlights the fact that even non-obese, overweight patients are at risk of toxicity when their actual body weight instead of their ideal body weight for height is used for intravenous acyclovir dose calculation.
PubMed: 38234392
DOI: 10.7759/cureus.52367 -
Scientific Reports Sep 2023The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid...
The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid crystals are proposed as a new ophthalmic drug delivery system. Acyclovir was chosen as model drug for its solubility and its controlled release from cubic phase was achieved. We demonstrated the effortless application of lamellar phase on corneal surface and its ability to convert itself in cubic phase in situ. While the complex viscosity of lamellar phase was affected by temperature (5.1 ± 1.4 kPa·s at 25 °C and 0.12 ± 0.001 Pa·s at 35 °C, respectively), the cubic phase shown no changes in viscosity values and shear thinning behaviour at both temperatures and even in presence of the drug The degradation kinetic of drug-loaded cubic phase was slightly slower than the empty formulation, recording 27.92 ± 1.43% and 33.30 ± 3.11% of weight loss after 8 h. Ex vivo studies conducted on porcine eyeballs and isolated cornea confirmed the instantaneous transition to cubic phase, its ability to resist to gravity force, and forced dripping of simulated tear fluid. Histopathological investigation showed how treated cornea did not report changes in epithelial and stroma structures. In summary, lyotropic liquid crystals could represent an advantageous ophthalmic drug delivery system.
Topics: Animals; Swine; Liquid Crystals; Drug Delivery Systems; Solubility; Cornea; Acyclovir
PubMed: 37758768
DOI: 10.1038/s41598-023-42185-z -
Biomedicine & Pharmacotherapy =... Nov 2023The Amazonian species investigated in this research are commonly utilized for their anti-inflammatory properties and their potential against various diseases. However,...
The Amazonian species investigated in this research are commonly utilized for their anti-inflammatory properties and their potential against various diseases. However, there is a lack of scientifically supported information validating their biological activities. In this study, a total of seventeen ethanolic or aqueous extracts derived from eight Amazonian medicinal plants were evaluated for their activity against Herpes Simplex type 1 (HSV-1) and Chikungunya viruses (CHIKV). Cytotoxicity was assessed using the sulforhodamine B method, and the antiviral potential was determined through a plaque number reduction assay. Virucidal tests were conducted according to EN 14476 standards for the most potent extracts. Additionally, the chemical composition of the most active extracts was investigated. Notably, the LMLE10, LMBA11, MEBE13, and VABE17 extracts exhibited significant activity against CHIKV and the non-acyclovir-resistant strain of HSV-1 (KOS) (SI > 9). The MEBE13 extract demonstrated unique inhibition against the acyclovir-resistant strain of HSV-1 (29-R). Virucidal assays indicated a higher level of virucidal activity compared to their antiviral activity. Moreover, the virucidal capacity of the most active extracts was sustained when tested in the presence of protein solutions against HSV-1 (KOS). In the application of EN 14476 against HSV-1 (KOS), the LMBA11 extract achieved a 99.9% inhibition rate, while the VABE17 extract reached a 90% inhibition rate. This study contributes to the understanding of medicinal species native to the Brazilian Amazon, revealing their potential in combating viral infections that have plagued humanity for centuries (HSV-1) or currently lack specific therapeutic interventions (CHIKV).
PubMed: 37713986
DOI: 10.1016/j.biopha.2023.115476 -
Investigative and Clinical Urology Jan 2024The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency regularly update, revise, and develop new... (Review)
Review
The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency regularly update, revise, and develop new content for the Korean sexually transmitted infection (STI) guidelines. These professional bodies respond to changing epidemiological trends and evolving scientific evidence, and consider advances in laboratory diagnostics and research. The principal recommendations of the 2023 Korean STI guidelines in terms of viral infection follow: 1) If genital herpes recurs more than 4-6 times annually, suppressive therapy with acyclovir 400 mg orally 2 times/day or famciclovir 250 mg orally 2 times/day or valacyclovir 500 mg orally once a day (for patients with <10 episodes/year) or valacyclovir 1 g orally once daily (for patients with ≥10 episodes/year) is recommended to prevent recurrence; 2) molecular human papillomavirus (HPV) testing is not recommended as a routine test for STI status, nor for determination of HPV vaccination status; and 3) patients should inform their current sexual partners about anogenital warts because the types of HPV that cause such warts can be passed to partners. These guidelines will be updated every 5 years and will be revised when new knowledge on STIs becomes available and there is a reasonable need to improve the guidelines. Physicians and other healthcare providers can use the guidelines to assist in the prevention and treatment of STIs.
Topics: Humans; Herpes Genitalis; Valacyclovir; Papillomavirus Infections; Sexually Transmitted Diseases; Warts; Virus Diseases; Republic of Korea
PubMed: 38197746
DOI: 10.4111/icu.20230275 -
Journal of Pharmaceutical Sciences Aug 2023The pharmacopoeial test method "Intrinsic Dissolution" (Ph.Eur. 2.9.29) is used to study the rate of dissolution for powders of active pharmaceutical ingredients...
The pharmacopoeial test method "Intrinsic Dissolution" (Ph.Eur. 2.9.29) is used to study the rate of dissolution for powders of active pharmaceutical ingredients normalized by the surface area. Therefore, powders are compacted into a special metal die holder, which is immersed into a dissolution vessel of the dissolution test apparatus (described in Ph.Eur. 2.9.3). However, in some cases, the test cannot be performed because the compacted powder would not stay in the die holder when in contact with the dissolution medium. In this study, we investigated the removable adhesive gum (RAG) as an alternative to the official die holder. Intrinsic dissolution tests were carried out to exemplify the use of the RAG for this purpose. As model substances, acyclovir and its co-crystal with glutaric acid were used. The RAG was validated for compatibility, release of extractables, unspecific adsorption and the ability to block drug release through the covered surfaces. The results showed that the RAG leaked no unwanted substances, showed no adsorption of acyclovir and blocked its release from covered surfaces. The intrinsic dissolution tests revealed, as expected, a constant release of drug with a small standard deviation between replicates. It was possible to distinguish the acyclovir release from the co-crystal and from the pure drug compound. In conclusion, the findings of this study suggest to consider removable adhesive gum as an easy-to-use and inexpensive alternative to the compendial die holder in intrinsic dissolution tests.
Topics: Solubility; Powders; Drug Liberation; Drug Compounding; Tablets
PubMed: 36863562
DOI: 10.1016/j.xphs.2023.02.020 -
Frontiers in Public Health 2023Herpes zoster (HZ) causes significant morbidity, particularly in older adults. With the advent of a recombinant zoster vaccine, HZ is potentially preventable. However,...
Herpes zoster (HZ) causes significant morbidity, particularly in older adults. With the advent of a recombinant zoster vaccine, HZ is potentially preventable. However, data on HZ burden and healthcare utilization in primary care populations remains scarce. This study described the prevalence and healthcare utilization in managing HZ in a developed community. A retrospective database review was conducted across a cluster of 8 public primary care clinics in urban Singapore. Data of multi-ethnic Asian patients with a diagnosis code of "herpes zoster" from 2018 to 2020 was extracted from their electronic medical records. Socio-demographic, clinical, visitation, medical leave, prescription, and referral data were analyzed. A total of 2,987 out of 737,868 individuals were diagnosed with HZ over 3 years. The mean age was 59.9 (SD + 15.5) years; 49.2% were male; 78.5% Chinese, 12.2% Malay, and 4.1% Indian. The prevalence was 221, 224, 203 per 100,000 persons in 2018, 2019, and 2020, respectively. The 70 to 79-year age group had the highest prevalence (829/100,000) across 3 years. Oral acyclovir (median daily dose 4,000 mg; median duration 7 days) and topical acyclovir were prescribed in 71.6 and 47.6%, respectively. Analgesia prescribed were gabapentin (41.0%), paracetamol combinations (30.1%), oral NSAIDs (23.7%), opioids (6.0%), and tricyclic antidepressants (1.9%). Most individuals consulted only once (84.3%); 32.7% of them required medical leave and 5.6% had more than 7 days of absenteeism. HZ-related referrals to the hospital were required in 8.9% (4.9% emergency, 2.8% ophthalmology). The findings of this study suggest a need for HZ vaccination among older age groups. Visitation and referral rates were low. The use of topical acyclovir was uncovered, and further research should evaluate the underlying reasons, benefits, and harms of such practice. The use of analgesia combinations may be explored further.
Topics: Humans; Male; Aged; Middle Aged; Child, Preschool; Female; Retrospective Studies; Urban Population; Prevalence; Herpes Zoster; Herpesvirus 3, Human; Herpes Zoster Vaccine; Patient Acceptance of Health Care; Acyclovir; Primary Health Care
PubMed: 37780417
DOI: 10.3389/fpubh.2023.1213736 -
Pharmaceutics Aug 2023Acyclovir (ACV) controls cutaneous herpes, genital herpes, herpes keratitis, varicella zoster, and chickenpox. From previously reported ACV formulations, we continued to...
Mechanistic of Vesicular Ethosomes and Elastic Liposomes on Permeation Profiles of Acyclovir across Artificial Membrane, Human Cultured EpiDerm, and Rat Skin: In Vitro-Ex Vivo Study.
Acyclovir (ACV) controls cutaneous herpes, genital herpes, herpes keratitis, varicella zoster, and chickenpox. From previously reported ACV formulations, we continued to explore the permeation behavior of the optimized ACV loaded optimized ethosome (ETHO2R) and elastic liposome (ELP3R) and their respective carbopol gels across artificial membrane, cultured human EpiDerm, and rat skin. Transepidermal water loss (TEWL), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and atomic force microscopy (AFM) were used to investigate the mechanistic perspective of permeation behavior. The size values of reformulated ELP3-R and ETHO2-R were observed as 217 and 128 nm, respectively (close to previous report), whereas their respective gels showed as 231 and 252 nm, respectively. ETHO2R showed high elasticity, %EE, and low vesicle size. These were investigated for the diffusion rate of the drug permeation (3 h) across the artificial membrane, cultured human EpiDerm, and rat skin. ETHO2GR showed the highest permeation flux (78.42 µg/cm/h), diffusion coefficient (8.24 × 10 cm/h), and permeation coefficient (0.67 × 10 cm/h) of ACV across synthetic membrane, whereas diffusion coefficient (2.4 × 10 cm/h) and permeation coefficient (0.8 × 10 cm/h) were maximum across EpiDerm for ETHO2GR. ETHO2R suspension showed maximized permeation flux (169.58 µg/cm/h) and diffusion rate (0.293 mg/cm/h), suggesting the rapid internalization of vesicles with cultured skin cells at low viscosity. A similar observation was revealed using rat skin, wherein the permeation flux (182.42 µg/cm/h), permeation coefficient (0.3 × 10 cm/h), and diffusion rate (0.315 mg/cm/h) of ETHO2R were relatively higher than ELP3R and ELP3GR. Relative small size (128 nm), low viscosity, ethanol-mediated ultra-deformability, high drug entrapment (98%), and elasticity (63.2) are associated with ETHO2R to provide remarkable permeation behavior across the three barriers. The value of TEWL for ETHO2R (21.9 g/mh) was 3.71 times higher than untreated control (5.9 g/mh), indicating ethanol-mediated maximized surficial skin lipid perturbation at 3 h of application, whereas the respective ETHO2GR-treated rat skin had TEWL value (18.6 g/mh) slightly lower than ETHO2R due to gel-based hydration into the skin. SEL, CLSM, and AFM provided a mechanistic perspective of ETHO2R and ELP3R-mediated permeation across rat skin and carrier-mediated visualization (skin-vesicle interaction). AFM provided detailed nanoscale surface roughness topographical parameters of treated and untreated rat skin as supportive data to SEM and CLSM. Thus, ethosomes ETHO2R and respective gel assisted maximum permeation of ACV across rat skin and cultured human EpiDerm to control cutaneous herpes infection and herpes keratitis.
PubMed: 37765159
DOI: 10.3390/pharmaceutics15092189 -
International Journal of Pharmaceutics Aug 2023Successful treatment of herpes simplex viruses is currently limited by a lack of effective topical drugs. Commonly used topical acyclovir products only reduce the...
Successful treatment of herpes simplex viruses is currently limited by a lack of effective topical drugs. Commonly used topical acyclovir products only reduce the duration of lesions by a few days. Optimizing topical formulations to achieve an enhanced acyclovir solubility and penetration could increase the efficacy of topically applied acyclovir, but new formulations need to show reliable acyclovir delivery into at least the epidermis/dermis and need to provide sustained acyclovir release for extended time periods. The aim of this study was to compare pharmacokinetic data from in vitro permeation testing (IVPT) and preclinical dermal open flow microperfusion (dOFM) experiments regarding the penetration behavior of different acyclovir formulations relative to the reference product Zovirax® 5% cream. Four test formulations that delivered the best penetration data in IVPT were further tested using continuous dOFM in vivo dermal sampling. The use of dOFM identified one of the four tested formulations to perform significantly better than the other three tested formulations and the reference product. In vivo dOFM data showed differences in the dermal acyclovir concentration that had not been detected by using IVPT. Improved acyclovir delivery to the dermis was likely achieved by the new formulation that uses a much lower drug load compared to the reference product. This optimized formulation was able to achieve a dermal concentration similar to oral application and can thus provide the opportunity of more efficacious topical HSV-1 treatment with less side effects than oral systemic treatment.
Topics: Acyclovir; Skin Absorption; Administration, Cutaneous; Administration, Topical; Herpesvirus 1, Human; Antiviral Agents
PubMed: 37495025
DOI: 10.1016/j.ijpharm.2023.123269 -
BMJ Open Jul 2023Congenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no...
Universal screening programme for cytomegalovirus infection in the first trimester of pregnancy: study protocol for an observational multicentre study in the area of Barcelona (CITEMB study).
INTRODUCTION
Congenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no universal screening programme for cCMV has been implemented in Spain. A recent study has shown that early treatment with valaciclovir, initiated in the first trimester and before the onset of signs in the fetus, reduces the risk of fetal infection. This finding favours the implementation of a universal screening programme for cCMV.The aim of this study is to evaluate the performance of a universal screening programme for cCMV during the first trimester of pregnancy in a primary care setting.
METHODS AND ANALYSIS
This is an observational multicentre cohort study. The study will be conducted in four primary care settings from the Northern Metropolitan Barcelona area and three related hospitals and will last 3 years and will consist of a recruitment period of 18 months.In their first pregnancy visit, pregnant women will be offered to add a CMV serology test to the first trimester screening tests. Pregnant women with primary infection will be referred to the reference hospital, where they will continue treatment and follow-up according to the clinical protocol of the referral hospital, which includes treatment with valacyclovir. A CMV-PCR will be performed at birth on newborns of mothers with primary infection, and those who are infected will undergo neonatal follow-up for at least 12 months of life.For the analysis, the acceptance rate, the prevalence of primary CMV infections and the CMV seroprevalence in the first trimester of pregnancy will be studied.
ETHICS AND DISSEMINATION
Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina Ethics Committee 22/097-P dated 27 April 2022.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Pregnancy Trimester, First; Cohort Studies; Seroepidemiologic Studies; Cytomegalovirus Infections; Pregnancy Complications, Infectious; Valacyclovir; Parturition; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 37474185
DOI: 10.1136/bmjopen-2023-071997 -
AIDS Research and Therapy Jul 2023To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR).
METHODS
A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections.
RESULTS
In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p < 0.001), while vision loss from CMVR continued to occur at the 12-month visit. The mean number of injections was 5.8 in the low-dose group and 5.4 in the intermediate-dose group. No significant differences were detected between the two groups (p > 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p < 0.05).
CONCLUSIONS
The efficacy and frequency of injections to treat CMVR in AIDS patients were not significantly different between low and intermediate doses. Zone I lesions were associated with a worse visual outcome, more injections and a higher occurrence rate of CMVR-related complications than lesions in other zones.
Topics: Humans; Antiviral Agents; Cytomegalovirus Retinitis; Acquired Immunodeficiency Syndrome; Prospective Studies; Retrospective Studies; HIV Infections; Ganciclovir; Treatment Outcome
PubMed: 37452370
DOI: 10.1186/s12981-023-00543-x