BackgroundThe elevated risk of serious complications like myocarditis and pericarditis after COVID-19 vaccination, especially in adolescent has been reported in some instances that need to be tested in regional populations and different ethnicity groups. The purpose of the study was to evaluate the side effects, hesitancy, and effectiveness outcomes following COVID-19 vaccination among children in Pakistan.MethodsThe study was planned using a cross-sectional design and data from Children and Adolescents (CA) was collected through a convenient sampling method using a validated questionnaire between February to July 2022. A total of 1,108 CA between the age of 12–18 years who received one or two doses of vaccine were selected and data were collected through direct interviews with respondents.ResultsThe results showed that among 99.8% of respondents who received the Pfizer COVID-19 vaccine, 72.3% of respondents were partially vaccinated (with one dose) while 27.7% were fully vaccinated (with two doses). COVID vaccination regime had a favorable safety profile in children as compared to adults. Vaccine hesitancy in children was reported to be 52.4% and the most common reasons for hesitance were the assumption that the vaccine is not safe (23.7%), the vaccine is not required (19.6%) and the vaccine is not effective (10.4%). The reported side effects were mainly mild (88.5%) followed by moderate (10.6%) and only 0.8% were of severe intensity. Post-vaccination local side effects of mild intensity were common with an onset of an average of 24 h (68%) and a duration of 2–3 days (60.6%). The reported side effects were significantly associated with gender (p = 0.00) while age had no significant effect on the occurrence of side effects. Overall, the vaccine was well tolerated by children and adolescents and was effective in preventing the reoccurrence of COVID-19 infection in 99.9% of participants.ConclusionCOVID-19 vaccine by Pfizer approved by the FDA for use in CA 12–18 years of age was well tolerated with a good safety profile and no serious adverse drug reactions were reported. The vaccine side effects were mild (88.5%) and lasted for an average of 2–3 days only (60.4%). The vaccine was effective in safeguarding Children against COVID-19 infection.

Objectives: Rasagiline, a drug for Parkinson’s disease is metabolized by CYP1A2 enzyme. The objective of the study was to investigate the influence of cytochrome P450 1A2 variants and smoking status of healthy individuals on the pharmacokinetics of rasagiline. Methods: A comparative, open label, interventional, single oral dose, pharmacokinetic study was performed on 108 healthy volunteers in UHS & UVAS, Lahore. Data collection was initiated in June 2016 and ended in January 2018. It was divided in three phases with 1, 2 and 5mg of rasagiline given to a group of 36 volunteers in each phase. Volunteers were sub-divided into six groups of AA smokers, AA non-smokers, AC smokers, AC non-smokers, CC smokers & CC non-smokers on the basis of genotyping and smoking status. Serial blood sampling was performed at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 & 12 hours after administration of rasagiline tablets. Plasma concentrations were determined using High Performance Liquid Chromatography (HPLC) method. Pharmacokinetic (PK) parameters were calculated using software (APO) pharmacological analysis. Results: Analysis of variance (ANOVA) showed significant difference between AA and CC groups. Multiple group comparison with post hoc Tukey’s revealed that AA-smokers had significantly less tmax (p<0.001), t1/2 (p<0.012), AUC (p<0.008) and highest Cl (p<0.001) as compared to CC-smokers. The trend was same across all three doses. Conclusion: The study concludes that the systemic metabolism of rasagiline is significantly increased in CYP1A2*AA variants while smoking status did not show consistent difference in PK parameters. Registered Trial: ISRCTN68198254 doi: https://doi.org/10.12669/pjms.38.3.4940 How to cite this:Bilal R, Ahmad NS, Zaffar S, Mazhar MU, Siddiqui WA, Tariq S. Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.4940 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan.Methods: Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM® using plasma concentration–time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks.Results: The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively.Conclusion: Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients.

A study was undertaken to investigate intestinal fat absorption in young children suffering from persistent diarrhoea in comparison with normal children of similar age. Absorption studies were performed using the breath test technique. Following oral administration of labelled triglyceride ([13C]trioctanoin), interval breath sampling was done for 6 h. The time course of excretion of 13CO2 in the breath was determined by isotope ratio mass spectrometric analysis of the gas samples. Excretion curves were constructed from the mean values of 13CO2 dose (per cent) excreted at each time point in breath samples and areas under the curve were determined for diarrhoea cases as well as for normal subjects. The time course of 13CO2 excretions and areas under the curve thus obtained were compared with each other and also with a reference study in which data from known malabsorption cases were available. The time of peak 13CO2 excretion in diarrhoea cases ranged from 60 to 240 min (average 150 min) compared with 120 to 270 min (average 195 min) for normal subjects, the level of peak of 13CO2 excreted/h was 4.8 +/- 1.2 per cent in diarrhoea cases and 5.3 +/- 2.3 per cent in normal children (NS). Mean areas under the curve for the two groups were 18.9 +/- 3.4 per cent for normal and 17.6 +/- 4.1 per cent dose 13CO2 excreted/6 h for diarrhoea cases (NS). These results indicate that intestinal absorption of medium chain triglycerides was not impaired significantly in the cases of persistent diarrhoea studied.

COVID-19 has rampaged across continents and has caused a devastating impact on life, economy, mobility, and health. Vaccines are still under clinical trials however there is no immediate solution or drug at hand for effective treatment. During this time, finding an unorthodox solution has become the need of the hour. Nigella sativa, commonly known as the black seed has been widely used as a traditional medicine in the past to fight illnesses. Chief compounds of N. Sativa seed, especially thymiquinone, α‐hederin, and nigellidine, could be developed into promising herbal drugs to combat COVID‐19 due to their therapeutic benefits. Extensive studies on N. Sativa have demonstrated its wide spectrum pharmacological properties which include immunomodulatory, analgesic, anti-inflammatory, antiviral, bronchodilatory, hepato-protective, reno-protective, gastro-protective, and antioxidant properties that can serve as a potent inhibitor for SARS-CoV-2. Furthermore, N. Sativa has also exhibited antidiabetic, antihypertensive, and antibacterial properties which would help COVID-19 patients with comorbidities. The objective of this review is aimed at establishing a link between the pharmacological benefits of N. Sativa and its potential to serve as a cure for COVID-19.