Lessons we learned during the past four challenging years in the COVID-19 era: pharmacotherapy, long COVID complications, and vaccine development.

About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail.

Ethosomes as dermal/transdermal drug delivery systems: applications, preparation and characterization.

Transdermal drug delivery systems (TDDSs) have gained substantial attention during the last decade. TDDS are versatile delivery systems in which active components are delivered to skin for local effects or systemic delivery of active pharmaceutical through the skin. Overcoming stratum corneum is the most challenging step of delivering drugs through the skin. Lipid-based vesicular delivery systems due to the capability of the delivery of both hydrophilic and hydrophobic drugs are becoming more popular during the recent years. Ethosomes are innovative, biocompatible, biodegradable and non-toxic form of lipid-based vesicles that efficiently enable to entrap drugs of various physicochemical properties. These are other forms of liposome which contain high amounts of ethanol in their structure that enabling ethosomes to efficiently penetrate through deeper layers of skin. Ethosomes have various compositions based on their type but are mainly composed of phospholipids, ethanol, water and the active components. Ethosomes are easily manufactured and they are superior compared to liposomes in terms of different aspects due to the presence of ethanol. The purpose of this review is to thoroughly focus on various aspects of ethosomes, including mechanism of penetration, advantages and disadvantages, characterisation and applications.

The association between estrogen receptor 2 gene polymorphism and complexity of coronary artery disease: an analysis in elective percutaneous coronary intervention patients.

BACKGROUND: One of the most common causes of death in the world is coronary artery disease (CAD). Estrogen, the most important early sex hormones in women, plays an important role in the risk reduction of cardiovascular disease (CVD). Expression of estrogen as well as its receptors including estrogen receptor alpha (ER1) and estrogen receptor beta (ER2) might have an association with the severity or the complexity of CAD. Since most articles have focused on the relationship between ER1 gene polymorphism and CAD, in this study, we aimed to evaluate the association of two ER2 gene polymorphisms, rs4986938 (AluI) and rs1256049 (RsaI), with the severity of CAD. METHODS: 148 patients with confirmed CAD who underwent elective percutaneous coronary intervention (PCI) were included in this study. Blood samples were collected before coronary angiography and ER2 gene polymorphisms were analyzed by the PCR-RFLP method. The STNTAX Score (SS), grading system for CAD complexity, was evaluated by an interventional cardiologist who was blinded to other data. RESULTS: 110 men and 38 women were participated in this study. Our results revealed a statistically significant relationship between SS and rs4986938 polymorphism of ER2 in men. In contrast, there was no association between rs1256049 genotypes and SS after performing regression analysis. CONCLUSIONS: Besides to the estrogen level, the genetic variation of its receptors might play an important role in the severity or the complexity of CAD. According to our results, rs4986938 polymorphism of ER2 gene may assert a pivotal role in the severity of CAD in men; however, this assumption needs to be proved in studies with a larger population.

Cyproterone acetate-loaded nanostructured lipid carriers: effect of particle size on skin penetration and follicular targeting.

Cyproterone acetate (CPA) is used to treat various skin disorders such as acne, hirsutism, and alopecia. Due to the limited skin penetration of CPA, nanostructured lipid carriers (NLCs) with different size ranges were considered in this study in order to enhance skin penetration and to target hair follicles. Drug loading, drug release and morphological assessment were evaluated for each targeted size (100, 300, and 600 nm). Ex vivo skin penetration was also investigated using Franz diffusion cells. Finally, in vivo follicular targeting was evaluated using rhodamine B-loaded micro and nanoparticles. Results revealed that 60-85% of drug was slowly released from lipid nanoparticles within 72 h. CPA-NLC with average diameter of 600 nm had better penetration and deposition in dermis-epidermis layer, also CPA-NLC 100 and 300 nm significantly increased drug penetration in dermis-epidermis in comparison to free CPA. Follicular targeting results revealed that NLC 300 nm had the best accumulation capacity in hair follicles. CPA-NLC with average diameter of 300 nm could be a promising topical novel drug delivery system for specific targeting of hair follicles and sebaceous glands to treat androgenic skin disorders such as acne, hirsutism, and alopecia.

Different therapeutic approaches in melasma: advances and limitations.

Melasma is a chronic hyperpigmentation skin disorder that is more common in the female gender. Although melasma is a multifactorial skin disorder, however, sun-exposure and genetic predisposition are considered as the main etiologic factors in melasma occurrence. Although numerous topical and systemic therapeutic agents and also non-pharmacologic procedural treatments have been considered in melasma management, however, the commonly available therapeutic options have several limitations including the lack of sufficient clinical effectiveness, risk of relapse, and high rate of unwanted adverse drug reactions. Recruitment of nanotechnology for topical drug delivery in melasma management can lead to enhanced skin penetration, targeted drug delivery to the site of action, longer deposition at the targeted area, and limit systemic absorption and therefore systemic availability and adverse drug reactions. In the current review, first of all, the etiology, pathophysiology, and severity classification of melasma have been considered. Then, various pharmacologic and procedural therapeutic options in melasma treatment have been discussed. Afterward, the usage of various types of nanoparticles for the purpose of topical drug delivery for melasma management was considered. In the end, numerous clinical studies and controlled clinical trials on the assessment of the effectiveness of these novel topical formulations in melasma management are summarized.

Preparation and characterization of artemether-loaded niosomes in Leishmania major-induced cutaneous leishmaniasis.

Cutaneous leishmaniasis is the most prevalent form of leishmaniasis worldwide. Although various anti-leishmanial regimens have been considered, due to the lack of efficacy or occurrence of adverse reactions, design and development of novel topical delivery systems would be essential. This study aimed to prepare artemether (ART)-loaded niosomes and evaluate their anti-leishmanial effects against Leishmania major. ART-loaded niosomes were prepared through the thin-film hydration technique and characterized in terms of particle size, zeta potential, morphology, differential scanning calorimetry, drug loading, and drug release. Furthermore, anti-leishmanial effect of the preparation was assessed in vitro and in vivo. The prepared ART-loaded niosomes were spherical with an average diameter of about 100 and 300 nm with high encapsulation efficiencies of > 99%. The results of in vitro cytotoxicity revealed that ART-loaded niosomes had significantly higher anti-leishmanial activity, lower general toxicity, and higher selectivity index (SI). Half-maximal inhibitory concentration (IC50) values of ART, ART-loaded niosomes, and liposomal amphotericin B were 39.09, 15.12, and 20 µg/mL, respectively. Also, according to the in vivo study results, ART-loaded niosomes with an average size of 300 nm showed the highest anti-leishmanial effects in animal studies. ART-loaded niosomes would be promising topical drug delivery system for the management of cutaneous leishmaniasis.

A Brief Review of Pharmacokinetic Assessments of Vancomycin in Special Groups of Patients with Altered Pharmacokinetic Parameters.

Vancomycin is considered the drug of choice against many Gram-positive bacterial infections. Therapeutic drug monitoring (TDM) is essential to achieve an optimum clinical response and avoid vancomycin-induced adverse reactions including nephrotoxicity. Although different studies are available on vancomycin TDM, still there are controversies regarding the selection among different pharmacokinetic parameters including trough concentration, the area under the curve to minimum inhibitory concentration ratio (AUC24h/MIC), AUC of intervals, elimination constant, and vancomycin clearance. In this review, different pharmacokinetic parameters for vancomycin TDM have been discussed along with corresponding advantages and disadvantages. Also, vancomycin pharmacokinetic assessments are discussed in patients with altered pharmacokinetic parameters including those with renal and/or hepatic failure, critically ill patients, patients with burn injuries, intravenous drug users, obese and morbidly obese patients, those with cancer, patients undergoing organ transplantation, and vancomycin administration during pregnancy and lactation. An individualized dosing regimen is required to guarantee the optimum therapeutic responses and minimize adverse reactions including acute kidney injury in these special groups of patients. According to the pharmacoeconomic data on vancomycin TDM, pharmacokinetic assessments would be cost-effective in patients with altered pharmacokinetics and are associated with shorter hospitalization period, faster clinical stability status, and shorter courses of inpatient vancomycin administration.

Update on the effectiveness of COVID-19 vaccines on different variants of SARS-CoV-2.

It has been more than three years since the first emergence of coronavirus disease 2019 (COVID-19) and millions of lives have been taken to date. Like most pandemics caused by viral infections, massive public vaccination is the most promising approach to cease COVID-19 infection. In this regard, several vaccine platforms including inactivated virus, nucleic acid-based (mRNA and DNA vaccines), adenovirus-based, and protein-based vaccines have been designed and developed for COVID-19 prevention and many of them have received FDA or WHO approval. Fortunately, after global vaccination, the transmission rate, disease severity, and mortality rate of COVID-19 infection have diminished significantly. However, a rapid increase in COVID-19 cases due to the omicron variant in vaccinated countries has raised concerns about the effectiveness of these vaccines. In this review, articles published between January 2020 and January 2023 were reviewed using PubMed, Google Scholar, and Web of Science search engines with appropriate related keywords. The related papers were selected and discussed in detail. The current review mainly focuses on the effectiveness and safety of COVID-19 vaccines against SARS-CoV-2 variants. Along with discussing the available and approved vaccines, characteristics of different variants of COVID-19 have also been discussed in brief. Finally, the currently circulating COVID-19 variant i.e Omicron, along with the effectiveness of available COVID-19 vaccines against these new variants are discussed in detail. In conclusion, based on the available data, administration of newly developed bivalent mRNA COVID-19 vaccines, as booster shots, would be crucial to prevent further circulation of the newly developed variants.

Simvastatin-Loaded Nanostructured Lipid Carriers as Topical Drug Delivery System for Wound Healing Purposes: Preparation, Characterization, and In Vivo Histopathological Studies.

Purpose: Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used drug to reduce total cholesterol and low-density lipoprotein (LDL) levels. Furthermore, several mechanisms showed the wound-healing potential of statins, especially simvastatin. Simvastatin is a lipophilic drug, therefore, it has low water solubility with limited skin permeability potential. In this regard, nanostructured lipid carriers (NLCs) were recruited as novel topical drug delivery systems to enhance skin adhesion and film formation, maintain skin integrity, sustain the release of simvastatin, and prolong simvastatin skin deposition to help pressure ulcers healing and regeneration. Methods: NLCs were fabricated using the solvent diffusion evaporation technique. Drug loading, in vitro drug release, and morphological assessment on the optimized formulation were considered. Furthermore, in vivo effect of simvastatin-loaded NLCs gel on pressure ulcer healing was assessed using a rat skin model. Histopathological assessments were compared with conventional simvastatin gel and drug-free NLCs gel. Results: Simvastatin-loaded NLC with an average diameter of 100 nm was considered as the optimum formulation. According to the results entrapment efficiency of simvastatin within the NLCs was about 99.4%. Drug release studies revealed sustained drug release from NLCs in which about 87% of the drug was slowly released during 48 hours. Animal study results confirmed that simvastatin-loaded NLCs gel has better efficacy on pressure ulcers and could significantly reduce inflammation, and promote skin regeneration compared to both drug-free NLCs and conventional simvastatin gels. Conclusion: Simvastatin-loaded NLCs with an average particle size of 100 nm would be a promising novel topical drug delivery system with sustained drug release potential for pressure ulcer treatment.

Optimization, characterization, and follicular targeting assessment of tretinoin and bicalutamide loaded niosomes.

Acne vulgaris, a prevalent skin disorder among teenagers and young adults, can have numerous psychological consequences. Topical treatment of acne would be advantageous by reducing the risk of systemic adverse drug reactions. However, the major challenge would be skin penetration through the stratum corneum. Therefore, during this study, tretinoin (TRT) and bicalutamide (BCT) loaded niosomes with follicular targeting potential were fabricated through the thin film hydration technique. Formulation optimization was performed using the Design-Expert software and optimum formulation was characterized in terms of particle size, zeta potential, transmission electron microscopy, drug loading, and differential scanning calorimetry. In vivo follicular targeting was assessed using rhodamine B-loaded niosomes to follow the skin penetration pathways. The results showed that, the optimum formulation was spherical in shape and had an average diameter of 319.20 ± 18.50 nm and a zeta potential of - 29.70 ± 0.36 mV. Furthermore, entrapment efficiencies were 94.63 ± 0.50% and > 99% and loading capacities were 1.40 ± 0.01% and 1.48 ± 0.00% for BCT and TRT, respectively. According to the animal study results, the prepared niosomes with an average diameter of about 300 nm showed significant accumulation in hair follicles. It seems that the designed niosomal BCT-TRT co-delivery system would be promising in acne management with follicular targeting potential.

Pharmacokinetic assessment of vancomycin in critically ill patients and nephrotoxicity prediction using individualized pharmacokinetic parameters.

Introduction: Therapeutic drug monitoring (TDM) and pharmacokinetic assessments of vancomycin would be essential to avoid vancomycin-associated nephrotoxicity and obtain optimal therapeutic and clinical responses. Different pharmacokinetic parameters, including trough concentration and area under the curve (AUC), have been proposed to assess the safety and efficacy of vancomycin administration. Methods: Critically ill patients receiving vancomycin at Nemazee Hospital were included in this prospective study. Four blood samples at various time intervals were taken from each participated patient. Vancomycin was extracted from plasma samples and analyzed using a validated HPLC method. Results: Fifty-three critically ill patients with a total of 212 blood samples from June 2019 to June 2021 were included in this study. There was a significant correlation between baseline GFR, baseline serum creatinine, trough and peak concentrations, AUCτ, AUC24h, Cl, and Vd values with vancomycin-induced AKI. Based on trough concentration values, 66% of patients were under-dosed (trough concentration <15 µg/ml) and 18.9% were over-dosed (trough concentration ≥20 µg/ml). Also, based on AUC24h values, about 52.2% were under-dosed (AUC24h < 400 µg h/ml), and 21.7% were over-dosed (AUC24h > 600 µg h/ml) that emphasizes on the superiority of AUC-based monitoring approach for TDM purposes to avoid nephrotoxicity occurrence. Conclusion: The AUC-based monitoring approach would be superior in terms of nephrotoxicity prediction. Also, to avoid vancomycin-induced AKI, trough concentration and AUCτ values should be maintained below the cut-off points.

The necessity of early anti-inflammatory therapy initiation in cases with mild-to-moderate COVID-19: A personal experience from an attending pharmacist and his resident.

I am a professor and attending pharmacist in the field of pharmaceutical sciences and writer or co-author of at least 5 manuscripts about different aspects of COVID-19. More than 15 months from the first report of COVID-19, over 120 million people all over the world infected by this virus, and more than 2.5 million of them have died. Although different treatment approaches have been proposed, management of the COVID-19 patients is steal remained controversial. In this regard, I want to share my personal experience from the exposure to the coronavirus and the consequence of this infection on my health status. I am a 51 years old male, known case of hypertension, dyslipidemia, and chronic kidney disease. During working hours of colleagues in the Faculty of Pharmacy, I visited one of my colleagues in his office. After leaving the Faculty, my colleague declares that his RT-PCR test of COVID-19 is positive and it took 3 days for me to experience the first sign of the COVID-19 as fever. Many complications have occurred for me during the different stages of COVID-19 infection that I shared and explained in detail with the suggested pharmacotherapies. According to the pathophysiology of COVID-19 infection and my personal experience during COVID-19 infection, I want to emphasize the necessity of early initiation of anti-inflammatory agents including corticosteroids and colchicine in high-risk patients with mild-to-moderate COVID-19 pneumonia who shows respiratory system involvement, in order to prevent progression to the severe and critical stages of this disease.

A focused review on technologies, mechanisms, safety, and efficacy of available COVID-19 vaccines.

>20 months has been passed since the detection of the first cases of SARS-CoV-2 infection named COVID-19 from Wuhan city of China. This novel coronavirus spread rapidly around the world and became a pandemic. Although different therapeutic options have been considered and approved for the management of COVID-19 infection in different stages of the disease, challenges in pharmacotherapy especially in patients with moderate to severe COVID-19 and with underlying diseases have still remained. Prevention of infection through public vaccination would be the only efficient strategy to control the morbidity and mortality caused by COVID-19. To date, several COVID-19 vaccines using different platforms including nucleic acid-based vaccines, adenovirus-based vaccines, protein-based vaccines, and inactivated vaccines have been introduced among which many have received approval for prevention against COVID-19. In this comprehensive review, available COVID-19 vaccines have been discussed. The mechanisms, safety, efficacy, dosage, dosing intervals, possible adverse reactions, storage, and coverage of these four different vaccine platforms against SARS-CoV-2 variants have been discussed in detail and summarized in tabular format for ease of comparison and conclusion. Although each COVID-19 vaccine has various advantages and disadvantages over the others, accessibility and affordability of approved vaccines by the official health organizations, especially in developing countries, would be essential to terminate this pandemic. The main limitation of this study was the lack of access to the clinical data on available COVID-19 vaccines developed in Eastern countries since the data on their efficacy, safety, and adverse reactions were limited.

Artemether-loaded nanostructured lipid carriers: preparation, characterization, and evaluation of in vitro effect on Leishmania major.

BACKGROUND AND PURPOSE: Cutaneous leishmaniasis is a global health problem. The discovery of new and highly efficient anti-leishmanial treatments with lower toxicity is globally needed. The current study was carried out to evaluate the anti-leishmanial effects of artemether (ART) and ART-loaded nanostructured lipid carriers (ART-NLCs) against promastigotes and amastigotes of Leishmania major. EXPERIMENTAL APPROACH: Solvent diffusion evaporation technique was applied to prepare ART-NLCs. These nanoparticles were characterized using a particle size analyzer (PSA), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The antiparasitic activity on amastigote was assessed in J774 cell culture. The drug cytotoxicity on promastigote and macrophage was assessed using the MTT technique after 24 and 48 h and compared with NLCs, ART, and amphotericin B, as the control agents. The selectivity index was calculated for the agents. FINDINGS/RESULTS: The DLS and PSA techniques confirmed that ART-NLCs were homogenous in size with an average diameter of 101 ± 2.0 nm and span index of 0.9. The ART-NLCs significantly heighten the anti-leishmanial activity of ART (P < 0.001). The IC50 values of ART and ART-NLCs on promastigotes after 24 and 48 h were 76.08, 36.71 and 35.14, 14.81 µg/mL, respectively while they were calculated 53.97, 25.43 and 20.13, 11.92 for amastigotes. Also, ART-NLCs had the lowest cytotoxicity against macrophages. Furthermore, among the agents tested, ART-NLCs had the highest selectivity index. CONCLUSION AND IMPLICATIONS: ART-NLCs had lower cytotoxic effects than ART and amphotericin B, also its selectivity index was significantly higher. Based on the findings of the study, this formulation could be a promising candidate for further research into leishmaniasis treatment.

Psychiatric Adverse Drug Reactions and Potential Anti-COVID-19 Drug Interactions with Psychotropic Medications.

Coronavirus disease 2019 (COVID-19) management in patients with predisposing psychiatric disorders would be challenging due to potential drug-drug interactions (PDDIs) and precipitation of their disease severity. Furthermore, COVID-19 itself might precipitate or induce unpredicted psychiatry and neuropsychiatry complications in these patients. In this literature review study, the psychological impacts of COVID-19 and major psychiatric adverse drug reactions (ADRs) of COVID-19 treatment options have been discussed. A detailed Table has been provided to assess potential drug-drug interactions of COVID-19 treatment options with psychotropic medications to avoid unwanted major drug-drug interactions. Finally, potential mechanisms of these major drug-drug interactions and possible management of them have been summarized. The most common type of major PDDIs is pharmacokinetics. Hydroxychloroquine/chloroquine and lopinavir/ritonavir were the most involved anti-COVID-19 agents in these major PDDIs.

Drug-based therapeutic strategies for COVID-19-infected patients and their challenges.

Emerging epidemic-prone diseases have introduced numerous health and economic challenges in recent years. Given current knowledge of COVID-19, herd immunity through vaccines alone is unlikely. In addition, vaccination of the global population is an ongoing challenge. Besides, the questions regarding the prevalence and the timing of immunization are still under investigation. Therefore, medical treatment remains essential in the management of COVID-19. Herein, recent advances from beginning observations of COVID-19 outbreak to an understanding of the essential factors contributing to the spread and transmission of COVID-19 and its treatment are reviewed. Furthermore, an in-depth discussion on the epidemiological aspects, clinical symptoms and most efficient medical treatment strategies to mitigate the mortality and spread rates of COVID-19 is presented.

Potential of Nanoparticles as Permeation Enhancers and Targeted Delivery Options for Skin: Advantages and Disadvantages.

The topical route of administration has many advantages for the treatment of various skin disorders as well as cosmeceutical purposes. This route bypasses hepatic first-pass effect and systemic availability of many pharmaceuticals is limited to skin organelles such as hair follicles and so could avoid unwanted adverse reactions and increase the localized therapeutic effect. Despite such attributed advantages of the topical route, the most important challenge is skin barrier characteristics that should be overcome to obtain dermal or trans-dermal drug delivery. Different approaches have been recruited to overcome this barrier. In this review, different types of nanoparticles for skin permeation enhancement and targeted delivery to skin organelles are discussed. The potential mechanisms of each nanocarrier in permeation enhancement and dermal delivery are considered and finally, the most important advantages and disadvantages of each group are summarized.

COVID-19 outbreak: Challenges in pharmacotherapy based on pharmacokinetic and pharmacodynamic aspects of drug therapy in patients with moderate to severe infection.

The new coronavirus (COVID-19) was first detected in Wuhan city of China in December 2019. Most patients infected with COVID-19 had clinical presentations of dry cough, fever, dyspnea, chest pain, fatigue and malaise, pneumonia, and bilateral infiltration in chest CT. Soon COVID-19 was spread around the world and became a pandemic. Now many patients around the world are suffering from this disease. Patients with predisposing diseases are highly prone to COVID-19 and manifesting severe infection especially with organ function damage such as acute respiratory distress syndrome, acute kidney injury, septic shock, ventilator-associated pneumonia, and death. Till now many drugs have been considered in the treatment of COVID-19 pneumonia, but pharmacotherapy in elderly patients and patients with pre-existing comorbidities is highly challenging. In this review, different potential drugs which have been considered in COVID-19 treatment have been discussed in detail. Also, challenges in the pharmacotherapy of COVID-19 pneumonia in patients with the underlying disease have been considered based on pharmacokinetic and pharmacodynamic aspects of these drugs.

A simple and validated HPLC method for vancomycin assay in plasma samples: the necessity of TDM center development in Southern Iran.

BACKGROUND AND PURPOSE: Vancomycin is a glycopeptide antibiotic which is the drug of choice against methicillin-resistant Staphylococcus aureus. It has a narrow therapeutic index, and thus therapeutic drug monitoring (TDM), and clinical pharmacokinetic assessment are necessary in order to prevent adverse drug reactions such as nephrotoxicity. In this study, we aimed to develop a simple and validated HPLC method for vancomycin assay in order to establish a TDM center for patients admitted to the ICU of Nemazee Hospital in southern Iran. EXPERIMENTAL APPROACH: In this study, a brief review of different parameters and variables which could affect the sensitivity, selectivity of the validated HPLC method for vancomycin determination were considered. According to the previous studies a simple, fast, and the relatively low-cost method was established for vancomycin determination in plasma samples. FINDINGS/RESULTS: The developed HPLC assay indicated a calibration curve with R-square of > 0.999, acceptable selectivity, the accuracy of 90-105%, CV% of less than 15%, the limit of quantification of 1 µg/mL, and limit of detection of 300 ng/mL. Vancomycin trough level, the area under the curve, renal clearance, the volume of distribution, and elimination constant were measured in patients using this validated method. CONCLUSION AND IMPLICATIONS: Validated method for assay of vancomycin plasma levels was used to quantify vancomycin levels of four patients who were admitted to the ICU of Nemazee Hospital. According to the results, two of these patients showed lower levels than recommended therapeutic purposes while one of them showed a toxic level. According to the results, the TDM assessment of vancomycin is strongly recommended for patients who are hospitalized in ICU.

Major Neurologic Adverse Drug Reactions, Potential Drug-Drug Interactions and Pharmacokinetic Aspects of Drugs Used in COVID-19 Patients with Stroke: A Narrative Review.

Stroke has been considered as one of the underlying diseases that increases the probability of severe infection and mortality. Meanwhile, there are ongoing reports of stroke subsequent to COVID-19 infection. In this narrative paper, we reviewed major neurologic adverse drug reactions (ADRs) and pharmacokinetics of drugs which are routinely used for COVID-19 infection and their potential drug-drug interactions (PDDIs) with common drugs used for the treatment of stroke. It is highly recommended to monitor patients on chloroquine (CQ), hydroxychloroquine (HCQ), antiviral drugs, and/or corticosteroids about initiation or progression of cardiac arrhythmias, delirium, seizure, myopathy, and/or neuropathy. In addition, PDDIs of anti-COVID-19 drugs with tissue plasminogen activator (tPA), anticoagulants, antiaggregants, statins, antihypertensive agents, and iodine-contrast agents should be considered. The most dangerous PDDIs were interaction of lopinavir/ritonavir or atazanavir with clopidogrel, prasugrel, and new oral anticoagulants (NOACs).