Development and evaluation of sildenafil/glycyrrhizin-loaded nanofibers as a potential novel buccal delivery system for erectile dysfunction.

Erectile dysfunction (ED) is a growing health condition that needs safe and effective therapy. One of the main common treatments is sildenafil which is used in clinics for managing erectile dysfunction by enhancing the blood supply to the penis. In the current study, sildenafil was formulated as nanofibers and mixed with the root extract of Glycyrrhiza glabra (glycyrrhizin) as a natural sweetener to be administrated in the buccal cavity for enhanced drug bioavailability, rapid drug absorption and improved patient compliance. The formulated dual-loaded nanofibers were evaluated by measuring diameter, disintegration, drug loading efficiency, drug release profile, and in vitro cell viability assessment. The results showed that the sildenafil/glycyrrhizin-loaded fibers had a diameter of 0.719 ± 0.177 µm and lacked any beads and pores formation on their surfaces. The drug loading and encapsulation efficiency for sildenafil were measured as 52 ± 7 µg/mg and 67 ± 9 %, respectively, while they were 290 ± 32 µg/mg and 94 ± 10 %, respectively, for glycyrrhizin. The release rate of sildenafil and glycyrrhizin demonstrated a burst release in the first minute, followed by a gradual increment until a complete release after 120 min. The in vitro cell viability evaluation exhibited that the application of sildenafil and glycyrrhizin is safe upon 24-hour treatment on human skin fibroblast cells at all used concentrations (i.e., ≤ 1,000 and 4,000 µg/mL, respectively). However, the application of sildenafil-glycyrrhizin combination (in a ratio of 1:4) demonstrated more than 80 % cell viability at concentrations of ≤ 250 and 1000 µg/mL, respectively, following 24-hour cell exposure. Therefore, sildenafil/glycyrrhizin dual-loaded PVP nanofibers showed a potential buccal therapeutic approach for erectile dysfunction management.

Predicting Hydroxychloroquine Clearance in Healthy and Diseased Populations Using a Physiologically Based Pharmacokinetic Approach.

Hydroxychloroquine (HCQ), a congener of chloroquine, is widely used in prophylaxis and the treatment of malaria, and also as a cure for rheumatoid arthritis, systemic lupus erythematosus, and various other diseases. Physiologically based pharmacokinetic modeling (PBPK) has attracted great interest in the past few years in predicting drug pharmacokinetics (PK). This study focuses on predicting the PK of HCQ in the healthy population and extrapolating it to the diseased populations, i.e., liver cirrhosis and chronic kidney disease (CKD), utilizing a systematically built whole-body PBPK model. The time vs. concentration profiles and drug-related parameters were obtained from the literature after a laborious search and in turn were integrated into PK-Sim software for designing healthy intravenous, oral, and diseased models. The model's evaluation was performed using observed-to-predicted ratios (Robs/Rpre) and visual predictive checks within a 2-fold error range. The healthy model was then extrapolated to liver cirrhosis and CKD populations after incorporating various disease-specific pathophysiological changes. Box-whisker plots showed an increase in AUC0-t in liver cirrhosis, whereas a decrease in AUC0-t was seen in the CKD population. These model predictions may assist clinicians in adjusting the administered HCQ doses in patients with different degrees of hepatic and renal impairment.

Nanocrystallization Improves the Solubilization and Cytotoxic Effect of a Poly (ADP-Ribose)-Polymerase-I Inhibitor.

Olaparib (OLA) is an anticancer agent that acts by inhibiting the poly (ADP-ribose)-polymerase-I (PARP-I). Due to its low solubility and low permeability, it has been placed as a BCS Class-IV drug and hence its clinical use is limited. In this study, we develop the nanocrystals of OLA as a way to improve its solubility and other performances. The OLA-NCs were prepared by antisolvent precipitation method through homogenization and probe sonication technique using a novel amphiphilic polymeric stabilizer (Soluplus®). Particle characterization resulted approximately 103.13 nm, polydispersity-index was 0.104 with positive zeta-potential of +8.67 mV. The crystal morphology by SEM of OLA-NCs (with and without mannitol) exhibited nano-crystalline prism-like structures as compared to the elongated OLA-pure. The DSC, XRD and FTIR were performed to check the interaction of Soluplus, mannitol and OLA did not exhibit any physical interaction among the OLA, Soluplus® and mannitol that is indicated by the presence of parent wave number peak. Two-fold increased solubility of OLA was found in PBS with Soluplus® from the NCs (69.3 ± 6.2 µgmL−1) as compared to pure drug (35.6 ± 7.2 µgmL−1). In vitro release of drug from OLA-NCs was higher (78.2%) at 12 h at pH 6.8 and relatively lower (53.1%) at pH 1.2. In vitro cellular cytotoxicity and anticancer effects were examined on MCF-7 cells. OLA-NCs were found effectively potent to MCF-7 cells compared with OLA-pure with approximately less than half IC50 value during MTT assay. Estimation of p53, Caspase-3 and Caspase-9 in MCF-7 cells indicated that OLA-NCs have significantly (p < 0.05) increased their expressions. After single oral dose in rats, 12 h plasma drug concentration-time profile indicated approximately 2.06-, 2.29-, 2−25- and 2.62-folds increased Cmax, AUC0-12 h, AUC0-∞ and AUMC0-∞, respectively, from the NCs as compared to OLA-pure. Storage stability indicated that the OLA-NCs was physically and chemically stable at 4 °C, 25 °C and 40 °C up to 6-months. Overall, OLA-NCs were deliberated; its potential feasibility to overwhelm the formulation challenges related to poorly soluble drugs and its future clinical applications.

Development of a Curcumin-Loaded Lecithin/Chitosan Nanoparticle Utilizing a Box-Behnken Design of Experiment: Formulation Design and Influence of Process Parameters.

Curcumin (CUR) has impressive pharmacologic properties, including cardioprotective, neuroprotective, antimicrobial, and anticancer activity. However, the pharmaceutical application of CUR is limited due to its poor aqueous solubility and low bioavailability. The development of novel formulations has attracted considerable attention to the idea of applying nanobiotechnology to improve the therapeutic efficacy of these challenging compounds. In this study, CUR-loaded lecithin−chitosan nanoparticles (CUR/LCSNPs) were developed and optimized by the concentration of chitosan, lecithin, and stirring speed by a 3-factorial Box-Behnken statistical design, resulting in an optimal concentration of chitosan (A) and lecithin (B) with a 1200 rpm stirring speed (C), with applied constraints of minimal average particle size (Y1), optimal zeta potential (Y2), and maximum entrapment efficiency (%EE) (Y3). The mean particle size of the checkpoint formulation ranged from 136.44 ± 1.74 nm to 267.94 ± 3.72, with a zeta potential of 18.5 ± 1.39 mV to 36.8 ± 3.24 mV and %EE of 69.84 ± 1.51% to 78.50 ± 2.11%. The mean particle size, zeta potential, %EE, and % cumulative drug release from the optimized formulation were 138.43 ± 2.09 nm, +18.98 ± 0.72 mV, 77.39 ± 1.70%, and 86.18 ± 1.5%, respectively. In vitro drug release followed the Korsmeyer−Peppas model with Fickian diffusion (n < 0.45). The optimized technique has proven successful, resulting in a nanoformulation that can be used for the high loading and controlled release of lipophilic drugs.

Vitamin D serum level predicts stroke clinical severity, functional independence, and disability-A retrospective cohort study.

Background: Stroke is a leading cause of mortality and disability and one of the most common neurological conditions globally. Many studies focused on vitamin D as a stroke risk factor, but only a few focused on its serum level as a predictor of stroke initial clinical severity and recovery with inconsistent results. The purpose of this study was to assess the relationship between serum vitamin D levels and stroke clinical severity at admission and functional independence and disability at discharge in Saudi Arabia. Methodology: A retrospective cohort study of adult ischemic stroke patients who had their vitamin D tested and admitted within 7 days of exhibiting stroke symptoms at King Abdulaziz Medical City (KAMC) Jeddah, Saudi Arabia. Based on vitamin D level, the patients were categorized into normal [25(OH)D serum level ≥ 75 nmol/L], insufficient [25(OH)D serum level is 50-75 nmol/L], and deficient [25(OH)D serum level ≤ 50 nmol/L]. The primary outcome was to assess the vitamin D serum level of ischemic stroke patients' clinical severity at admission and functional independence at discharge. The National Institute of Health Stroke Scale (NIHSS) was used to assess the clinical severity, whereas the modified Rankin scale (mRS) was used to assess functional independence and disability. Results: The study included 294 stroke patients, out of 774, who were selected based on the inclusion and exclusion criteria. The mean age of the participants was 68.2 ± 13.4 years, and 49.3% were male. The patients' distribution among the three groups based on their vitamin D levels is: normal (n = 35, 11.9%), insufficient (n = 66, 22.5%), and deficient (n = 196, 65.6%). After adjusting for potential covariates, regression analysis found a significant inverse relationship of NIHSS based on 25(OH)D serum level (beta coefficient: -0.04, SE: 0.01, p = 0.003). Patients with deficient serum vitamin D level also had significantly higher odds of worse functional independence in mRS score [OR: 2.41, 95%CI: (1.13-5.16), p = 0.023] when compared to participants with normal vitamin D level. Conclusion: Low vitamin D levels were associated with higher severity of stroke at admission and poor functional independence and disability at discharge in patients with acute ischemic stroke. Further randomized clinical and interventional studies are required to confirm our findings.

Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines.

Abemaciclib (AC) is a novel, orally available drug molecule approved for the treatment of breast cancer. Due to its low bioavailability, its administration frequency is two to three times a day that can decrease patient compliance. Sustained release formulation are needed for prolong the action and to reduce the adverse effects. The aim of current study was to develop sustained release NSs of AC. Nanosponges (NSs) was prepared by emulsion-solvent diffusion method using ethyl-cellulose (EC) and Kolliphor P-188 (KP-188) as sustained-release polymer and surfactant, respectively. Effects of varying surfactant concentration and drug: polymer proportions on the particle size (PS), polydispersity index (PDI), zeta potential (ζP), entrapment efficiency (%EE), and drug loading (%DL) were investigated. The results of AC loaded NSs (ACN1-ACN5) exhibited PS (366.3-842.2 nm), PDI (0.448-0.853), ζP (-8.21 to -19.7 mV), %EE (48.45-79.36%) and %DL (7.69-19.17%), respectively. Moreover, ACN2 showed sustained release of Abemaciclib (77.12 ± 2.54%) in 24 h Higuchi matrix as best fit kinetics model. MTT assay signified ACN2 as potentials cytotoxic nanocarrier against MCF-7 and MDA-MB-231 human breast cancer cells. Further, ACN2 displayed drug release property without variation in the % release after exposing the product at 25 °C, 5 °C, and 45 °C storage conditions for six months. This investigation proved that the developed NSs would be an efficient carrier to sustain the release of AC in order to improve efficacy against breast cancer.

The relationship between hydroxychloroquine plasma concentration and COVID-19 outcomes in rheumatoid arthritis patients in Saudi Arabia.

Background: The drug hydroxychloroquine (HCQ) is widely used to treat rheumatoid arthritis (RA) and has been repurposed for the treatment of COVID-19. This study aims to determine whether HCQ concentration levels in individuals with RA alter the incidence of COVID-19 or its complications. Methods: We collected plasma samples from 13 individuals with confirmed rheumatoid arthritis (RA) to measure HCQ concentration levels. The study included individuals at least 18 years old who had been taking HCQ for at least six months at daily doses ranging from 200 to 400 mg. Results: The study enrolled a total of 13 RA patients. All patients were chronic HCQ users. Among the 13 patients, 7 patients were receiving HCQ at a dose of 200 mg per day, and 6 patients were receiving HCQ at a dose of 400 mg per day. COVID-19 confirmed cases accounted for approximately 46% of all patients. Half of the infected patients (n = 3) were taking a daily dose of 200 mg daily, while the other half were taking 400 mg daily. COVID-19 symptoms ranged from mild to moderate, and the intensity of the symptoms was not severe enough to necessitate hospitalization. COVID-19 symptoms in RA patients included headache, fever, fatigue, dry cough, and loss of taste or smell. Conclusions: Our findings indicated that there was no correlation between HCQ concentrations in rheumatoid arthritis patients and the occurrence of COVID-19 or its complications.

Application of hydrophilic polymers for the preparation of tadalafil solid dispersions: micromeritics properties, release and erectile dysfunction studies in male rats.

The objective of the present study was to improve the dissolution rate and aphrodisiac activity of tadalafil by using hydrophilic polymers. Solid dispersions were prepared by solvent evaporation-Rota evaporator using Koliphore 188, Kollidon® VA64, and Kollidon® 30 polymers in a 1:1 ratio. Prepared tadalafil-solid dispersions (SDs) evaluated for yield, drug content, micromeritics properties, physicochemical characterizations, and aphrodisiac activity assessment. The optimized SDs TK188 showed size (2.175 ± 0.24 µm), percentage of content (98.89 ± 1.23%), yield (87.27 ± 3.13%), bulk density (0.496 ± 0.005 g/cm3), true density (0.646 ± 0.003 g/cm3), Carr's index (23.25 ± 0.81), Hausner ratio (1.303 ± 0.003) and angle of repose (<25°). FTIR spectrums revealed tadalafil doesn't chemically interact with used polymers. XRD and DSC analysis represents TK188 SDs were in the amorphous state. Drug release was 97.17 ± 2.43% for TK188, whereas it was 32.76 ± 2.65% for pure drug at the end of 2 h with 2.96-fold increase in dissolution and followed release kinetics of Korsmeyer Peppa's model. MDT and DE were noted to be 17.48 minutes and 84.53%, respectively. Furthermore, TK188 SDs showed relative improvement in the sexual behavior of the male rats. Thus the developed SDs TK188 could be potential tadalafil carriers for the treatment of erectile dysfunction.

Boosting the Anticancer Activity of Sunitinib Malate in Breast Cancer through Lipid Polymer Hybrid Nanoparticles Approach.

In the current study, lipid-polymer hybrid nanoparticles (LPHNPs) fabricated with lipoid-90H and chitosan, sunitinib malate (SM), an anticancer drug was loaded using lecithin as a stabilizer by employing emulsion solvent evaporation technique. Four formulations (SLPN1-SLPN4) were developed by varying the concentration of chitosan polymer. Based on particle characterization, SLPN4 was optimized with size (439 ± 5.8 nm), PDI (0.269), ZP (+34 ± 5.3 mV), and EE (83.03 ± 4.9%). Further, the optimized formulation was characterized by FTIR, DSC, XRD, SEM, and in vitro release studies. In-vitro release of the drug from SPN4 was found to be 84.11 ± 2.54% as compared with pure drug SM 24.13 ± 2.67%; in 48 h, release kinetics followed the Korsmeyer-Peppas model with Fickian release mechanism. The SLPN4 exhibited a potent cytotoxicity against MCF-7 breast cancer, as evident by caspase 3, 9, and p53 activities. According to the findings, SM-loaded LPHNPs might be a promising therapy option for breast cancer.

Development of Apremilast Nanoemulsion-Loaded Chitosan Gels: In Vitro Evaluations and Anti-Inflammatory and Wound Healing Studies on a Rat Model.

Apremilast (APL) has profound anti-inflammatory and wound healing activity, alongside other dermal care. This study aims to develop APL-loaded NEs (ANE1-ANE5) using eucalyptus oil (EO) as the oil and Tween-80 and transcutol-HP (THP) as a surfactant and co-surfactant, respectively. The prepared NEs were then evaluated based on mean droplet size (12.63 ± 1.2 nm), PDI (0.269 ± 0.012), ZP (-23.00 ± 5.86), RI (1.315 ± 0.02), and %T (99.89 ± 0.38) and ANE4 was optimized. Further, optimized NEs (ANE4) were incorporated into chitosan gel (2%, w/v). The developed ANE4-loaded chitosan gel was then evaluated for pH, spreadability, in vitro diffusion, and wound healing and anti-inflammatory studies. Moreover, in vivo studies denoted improved anti-inflammatory and wound healing activity and represented a decrease in wound size percentage (99.68 ± 0.345%) for the APNE2 gel test compared to a negative control (86.48 ± 0.87%) and standard control (92.82 ± 0.34%). Thus, the formulation of ANE4-loaded chitosan gels is an efficient topical treatment strategy for inflammatory and wound healing conditions.

Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort.

OBJECTIVE: Hydroxychloroquine (HCQ) has been used during the coronavirus disease 2019 (COVID-19) pandemic because of its reported anti-viral activity. This study examined the association of chronic HCQ use with the incidence and complications of COVID-19. METHODS: This retrospective cohort study included adults with rheumatoid arthritis and/or systemic lupus erythematosus who visited rheumatology clinics in three tertiary hospitals in Riyadh, Saudi Arabia between January 2019 and December 2020. Patients were categorized into two groups based on HCQ use. Data were obtained from the electronic health record and by interviews with patients. The primary study objective was the incidence of COVID-19 and its complications from March 2020 to February 2021. RESULTS: Almost 11% of the study cohort was positive for COVID-19, and the incidence of COVID-19 was similar between HCQ users (11.11%) and nonusers (10.86%). Disease complication rates were similar in the study arms, and they mainly included fever, dry cough, fatigue, and breathing difficulty. CONCLUSIONS: This study revealed no significant association between chronic HCQ use and the incidence of COVID-19, and disease complications were similar in the study arms.

Association of Healthy Diet with Recovery Time from COVID-19: Results from a Nationwide Cross-Sectional Study.

The world is still in need of an effective therapy to treat coronavirus disease-19 (COVID-19). This cross-sectional study was conducted on COVID-19 survivors in Saudi Arabia to investigate the influence of a healthy diet on the recovery time from COVID-19. A questionnaire was developed to assess participants' dietary habits, based on the 2015 Dutch food-based dietary guidelines. A total of 738 COVID-19 survivors participated in the study, of whom 237 (32.1%) were hospitalized for COVID-19 treatment while 501 (76.9%) were not hospitalized, and 320 (43.4%) were females and 418 (56.6%) were males. Overall, no significant difference was noted in healthy diet score between males and females; however, this score was significantly lower for Saudis compared to non-Saudis. Among the non-hospitalized patients, eating a more healthy diet was associated with a shorter duration of recovery (p < 0.05) and was significantly affected by gender (15.8 ± 9.3 male vs. 12.1 ± 8.9 female; p < 0.001) and marital status (12.1 ± 8.4 singles vs. 13.7 ± 9.3 married vs. 16.1 ± 11.8 divorced; p < 0.05). In contrast, no significant correlation was found with age or BMI. In this study, a more healthy diet was associated with a shorter duration of recovery from COVID-19. However, further studies are needed to thoroughly investigate the relationship between diet and recovery time from COVID-19.

Validation and Cultural Adaptation of Explanatory Model Interview Catalogue (EMIC) in Assessing Stigma among Recovered Patients with COVID-19 in Saudi Arabia.

Stigma is a negative feeling affecting many patients with various health conditions, especially the contagious ones such as COVID-19. The Explanatory Model Interview Catalogue (EMIC) is one of the valid and reliable stigma-measuring tools; however, it has not been translated and validated in Arabic. Therefore, the aim of this study was to translate and validate the EMIC in Arabic among a sample of Arabic-speaking adults who recently recovered from COVID-19 in Saudi Arabia. The 12 items of the EMIC scale were forward- and backward-translated and reviewed by all authors to check the face and content validity prior to approving the final version of the Arabic 12-item EMIC. A total of 174 participants aged ≥18 years who contracted COVID-19 and recovered as of 29 July 2020 were interviewed. The Cronbach's alpha of the Arabic version of the 12-item EMIC was 0.79, indicating an acceptable level of internal consistency. Using principal component analysis with varimax rotation, two factors explained more than 60% of the variance of the translated EMIC scale. The mean EMIC score was 5.91, implying a low level of stigma among participants. Married participants (ß = 2.93; 95%CI 0.88 to 4.98, p = 0.005) and those with a family history of mental illness (ß = 2.38; 95%CI 0.29 to 4.46, p = 0.025) were more likely to have higher EMIC scores in comparison to their counterparts who were unmarried and had no family history of mental illness. On the contrary, older adults were less likely to have high EMIC scores (ß = -0.11; 95%CI -0.21 to -0.01, p = 0.03). Future studies with larger samples of patients with COVID-19 and various health conditions should be conducted to examine the validity and reliability of the Arabic version of the EMIC among different patient populations and to unveil the factors that may play a role in patients' feelings of stigmatization in this part of the world.

Design of Olmesartan Medoxomil-Loaded Nanosponges for Hypertension and Lung Cancer Treatments.

Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = -18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m2/g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly (p < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.

Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique.

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25-41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5-15%) and microcrystalline cellulose (10-60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0-∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs' product quality and performance.

Demographics, comorbidities, and outcomes among young and middle-aged COVID-19 patients in Saudi Arabia.

The impact of different sociodemographic and clinical characteristics on the COVID-19-related morbidity and mortality rates have been studied extensively around the world; however, there is a dearth of data on the impact of different clinical and sociodemographic variables on the COVID-19-related outcomes in Saudi Arabia. This study aimed to identify those at high risk of worse clinical outcomes, such as hospitalization and longer length of stay (LOS) among young and middle-aged adults (18 to 55 years). In this questionnaire-based cross-sectional study, 706 patients with real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 infection were interviewed. Patients' demographic characteristics, dietary habits, medical history, and lifestyle choices were collected through phone interviews. Patients with chronic health conditions, such as diabetes and hypertension, reported a higher rate of hospitalization, ICU admission, oxygen-support needs, and a longer period of recovery and LOS. Multiple logistic regression showed that diabetes, hypertension, and pulmonary disease (e.g., asthma and chronic obstructive pulmonary disease (COPD)) were associated with a higher risk of hospitalization and longer LOS. Multiple logistic regression showed that symptoms of breathlessness, loss of smell and/or taste, diarrhea, and cough were associated with a longer recovery period. Similarly, breathlessness, vomiting, and diarrhea were associated with higher rates of hospitalization. The findings of this study confirm the similarity of the factors associated with worse clinical outcomes across the world. Future studies should use more robust designs to investigate the impact of different therapies on the COVID-19-related morbidity and mortality in Saudi Arabia.

Development and evaluation of physiologically based pharmacokinetic drug-disease models for predicting captopril pharmacokinetics in chronic diseases.

The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator Simcyp was used as a modeling and simulation platform. The visual predictive checks and mean observed/predicted ratios (ratio(Obs/pred)) of the PK parameters were used for model evaluation. The developed disease models were successful in predicting captopril PK in all three stages of CKD (mild, moderate, and severe) and CHF, as the observed and predicted PK profiles and the ratio(obs/pred) for the PK parameters were in close agreement. The developed captopril PBPK models can assist in tailoring captopril dosages in patients with different disease severity (CKD and CHF).