Study of influence of Catha edulis (Khat) chewing on oral pharmacokinetics of irbesartan in rats using a newly developed HPLC-UV method.

Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 - 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% - 3.27% and 0.39-1.98% respectively) and accuracy (% recovery = 98.3 - 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.

Early oral switch to combined cefixime therapy for management of osteoarticular infections in pediatric sickle cell disease patients: A descriptive analysis.

BACKGROUND: The treatment of osteoarticular infections in pediatric patients with sickle cell disease (SCD) is a challenging task for the practitioner. The aim of this study is to evaluate cefixime for the treatment of osteoarticular infections in pediatric SCD patients by retrospective design. METHODS: This study was done in the pediatric hospital of King Saud Medical City, Riyadh, Saudi Arabia. The data was obtained from medical records of patients aged 1-16 years admitted between January 2019 to December 2020, diagnosed with SCD and received cefixime for the treatment of OI. A descriptive study for pediatric patients admitted between January 2019 to December 2020 diagnosed with sickle cell disease and diagnosed with osteoarticular infection. All patients were treated with cefixime. Medians and interquartile ranges (IQRs) were used for the descriptive analysis. RESULTS: A total of 260 patients were screened, and 51 cases [osteomyelitis (OM), n = 43, and septic arthritis (SA), n = 8] met the inclusion criteria. The median age of OM patients was 7 years, with males making up 67.4% of the cohort. The median length of IV antibiotics and hospital stays were 10 days and 11 days, respectively. The median total duration of antibiotic use was 37 and 25 days for OM and SA, respectively. The treatment success rate was 88% in OM cases and 100% in SA patients. Readmission was noted in 39.5% of the OM patients, while only 25% of the SA patients were recorded for reinfection. CONCLUSION: The study's findings revealed that Cefixime is a viable oral alternative for treating osteoarticular infection in pediatric SCD patients. Nonetheless, a prospective investigation is required to corroborate the findings of this study.

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data.

Introduction: Thrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients. Methodology: This retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24-48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms. Results: A total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94-2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88-1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88-2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83-2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23-2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79-5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26-6.80) and aHR = 3.9 (95% CI, 1.73-8.76), respectively. Conclusion: Among COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

Tocilizumab effectiveness in mechanically ventilated COVID-19 patients (T-MVC-19 Study): a multicenter real-world evidence.

BACKGROUND: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint. RESULTS: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16). CONCLUSIONS: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

Postpartum prophylaxis of venous thromboembolism with anticoagulation: A case report.

Although there is a remarkably high risk of venous thromboembolism (VTE) during pregnancy and postpartum, a cautious approach is needed while initiating therapeutic and prophylactic anticoagulant therapy. The merits of heparin for thromboprophylaxis in postpartum patients are exaggerated, and its risk is generally overlooked. This study aimed to report the inappropriate use of anticoagulants in postpartum patients. The patient in this report was a 31-year-old healthy woman who had had a normal spontaneous vaginal delivery and visited the hospital a 3-day history of small itchy blisters at the enoxaparin injection sites. An examination revealed class II obesity. The Naranjo Scale assessment showed the possibility of an enoxaparin-induced hypersensitivity reaction. The clinical care team decided to discontinue the heparin. A follow-up examination did not show any signs of VTE. Although many pregnant and postnatal women might need VTE prophylaxis, routine anticoagulation for such a population is not essential. Clinicians should weigh the risks versus benefits to avoid any adverse drug reactions that may occur with this class of medication.