Epidemiological and Clinical Characteristics of COVID-19: A Retrospective Multi-Center Study in Pakistan.

The emergence of a pathogen responsible for a mysterious respiratory disease was identified in China and later called a novel coronavirus. This disease was named COVID-19. The present study seeks to determine the epidemiological and clinical characteristics of COVID-19 in Pakistan. This report will exhibit a linkage between epidemiology and clinical aspects which in turn can be helpful to prevent the transmission of the virus in Pakistan. A retrospective, multiple center study was performed by collecting the data from patients' with their demographics, epidemiological status, history of co-morbid conditions, and clinical manifestations of the disease. The data was collected from 31 public-sector and 2 private hospitals across Pakistan by on-field healthcare workers. A Chi-square test was applied to assess the relationship between categorical data entries. A total of 194 medical records were examined. The median age of these patients was found to be 34 years. A total of 53.6% active cases were present including 41.2% males and 12.4% females till the end of the study. Adults accounted for most of the cases (94.3%) of COVID-19. Fever (86.60%), cough (85.05%), fatigue (36.60%), dyspnea (24.74%), and gastrointestinal discomfort (10.31%) were among the most frequently reported signs and symptoms by the patients. However, 4.12% of the total patient population remained asymptomatic. The median duration of hospital stay was found to be 14 (0-19) days. The earliest source of the spread of the virus may be linked to the foreigners traveling to Pakistan. Spread among men was more as compared to women. A few cases were found to be positive, due to the direct contact with pets or livestock. Hypertension (7.73%), diabetes (4.64%), cardiovascular conditions (2.58%) were the most common co-morbidities. The percentage mortality was 2.50% with the highest mortality among elders.

Evaluation of gender difference in pharmacokinetics of Candesartan cilexetil in the fasted state by RP-HPLC: A single dose comparative study.

To compare the pharmacokinetics of candesartan cilexetil in healthy male and female volunteers in order to identify possible influence of gender and to improve therapeutic outcomes, an HPLC method for the quantification of candesartan cilexetil was developed and validated. Total of 16 volunteers (8 male and 8 female) were registered. Candesartan cilexetil 16 mg was administered orally to all the volunteers and blood samples were collected at different time intervals between 0-72 hours. Plasma was separated and analysed by HPLC method. Pharmacokinetic parameters were calculated by using APO software MW/PHARM version 3.02 and compared in male and female volunteers. The developed HPLC method fulfils the criteria for linearity, accuracy and precision described in EMA guideline. The values for absorption rate constant (Ka), maximum plasma concentration (Cmax), volume of distribution (Vd) and Clearance (CL) were similar in male and female volunteers. No influence of gender was observed on overall pharmacokinetics of candesartan cilexetil. Therefore, no need for dose optimization while administering candesartan cilexetil in male and female patients was found based on the results of this study.

Development of paracetamol-caffeine co-crystals to improve compressional, formulation and in vivo performance.

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90-97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and Cmax. A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

Polymeric microspheres of okra mucilage and alginate for the controlled release of oxcarbazepine: In vitro &in vivo evaluation.

Oxcarbazepine-loaded alginate/okra pods mucilage microspheres were prepared through inotropic gelation technique for the sustained release of oxcarbazepine. The drug encapsulating efficiency of these microspheres was found 76.22 ±â€¯0.01% to 90.57 ±â€¯0.02% and their average particle sizes were 496 µm ±â€¯0.41 to 692 µm ±â€¯0.22. These microspheres were characterized in terms of swelling capacity, FTIR, DSC and SEM analysis. The in vitro drug release from these microspheres was followed sustained release (Korsemeyer - Peppas model) pattern (R2 = 0.9552-0.9906) and value of n > 1 showed that drug released by anomalous (non-Fickian) diffusion. The in vivo studies showed that there were highly significant difference with p < 0.001 in the pharmacokinetic parameters (Cmax, t½, AUC0-∞, Ke), when oxcarbazepine was formulated in form of polymeric microspheres as compared to pure drug.

RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.

Assessment of sex differences in Pharmacokinetics of carvedilol in human.

Carvedilol is an anti-hypertensive agent capable of blocking both alph (α) and beta (ß) receptors used to preclude cardiac arrhythmias and angina. The study was designed to evaluate the Pharmacokinetics of carvedilol in human male and female volunteers. Healthy male and female (twenty each) volunteers were finalized for the study after preliminarily clinical examination. Blood samples were collected at specific time intervals after giving an oral dose of 12.5mg carvedilol, separated the plasma and placed at -80°C until analysis. Estimation of carvedilol in human plasma was accomplished by High performance liquid chromatographic (HPLC) method using fluorescent detector. Plasma concentration-time curve was used for calculation of pharmacokinetic parameters using two-compartment open model. Mean (SD) values of AUC and Cmax 0.076±0.021ßg.h/ml and 0.024±0.005ßg/mL, respectively) in male differ significantly (P<0.05) from the female 0.197±0.042ßg.h/ml and 0.048±0.02ßg/mL, respectively). Overall, bioavailability of carvedilol was somewhat higher in females than in males, but these differences could be expounded by the lower body weight of female. Conversely, no significant differences were found for tmax, clearance and half-life in male and female. Moreover the ethnicity had significant impact on the Pharmacokinetics of carvedilol in human.

Bioequivalence study of montelukast tablets in healthy Pakistani volunteers.

Montelukast is a leukotrien receptor antagonist used for asthma treatment. Objective of this study was to evaluate the bioequivalence of two montelukast 10mg tablets, Innovator drug (Singulair) as reference and other locally manufactured drug (Montiget) in 12 healthy volunteers. It was randomized, single dose, two-period crossover study with 1 week washout period. Blood samples (4-5 ml) were collected before and after drug administration and plasma was separated for analysis. Concentrations of montelukast at different time intervals were determined by validated UV-HPLC method at 345nm wavelength. Bioequivalence was assessed by using non compartmental approach and also calculated the 90% confidence interval of the least-squared pharmacokinetic parameters (Cmax, AUC0-t and AUC0-OO). On average, Cmax, AUC0-t, AUC0-inf, was 2.35µg/mL, 1.28µg.h./ml, 1.67µg.h./ml, for innovator drug and 2.53µg/mL, 1.53µg.h./ml, 1.96µg.h./ml, for test drug, respectively. Confidence interval (90%) for Cmax, AUC0-t and AUC0-inf was 89-97%, 85-91% and 81-98% respectively. No statistical difference was found between the Cmax and AUC values of test and reference drugs. The confidence intervals for Cmax, AUC0-t and AUC0-OO are fully laid within the acceptable range of FDA (80-125%), thus two formulations are considered to be bioequivalent.

Gender differences on bioavailabity of ofloxacin.

BACKGROUND: The fluoroquinolones are currently enjoying extensive worldwide clinical applications because of their good bioavailability and pharmacokinetic profile. Investigation into several aspects of the pharmacokinetic of all clinically relevant fluoroquinolones, have been carried out notably in Europe, USA and Japan. In view of the 'geonetical' (geographical influences on genetics-pharmacogenetics) differences, it is important that for the optimal therapeutic outcome, biodisposition studies on drugs are better conducted in the population and environments where wide and extensive use of the drug is anticipated. The Objectives of study were to see the pharmacokinetic parameters in healthy young male and female volunteers. This comparative study was conducted King Edward Medical University, Lahore, Pakistan, from July 2005 to December 2005. METHOD: In Pakistan where the use of antibiotics is more frequent by the general practitioners it is important to elucidate certain dose parameters it is also noticed that side effects are more in females than males so present study is conducted to calculate any differences in bioavailability on the basis of sex. The pharmacokinetic parameters of ofloxacin were determined in each of the clinically health eight young girls and boys (mean age 23.9 and 25.1 years, respectively) following a single oral dose of 400 mg tablet. The method adopted was microbiological assay. RESULTS: The blood samples collected at predetermined time intervals after drug administration revealed almost twice as high concentration of the drug in plasma of the girls than that in the boys. The pharmacokinetic parameters revealed significantly (p < 0.01) higher values for area under curve (AUC) and C(max) and lower total body clearance (TBC) and volume of distribution in the girls than in the boys. CONCLUSION: The gender differences in pharmacokinetic parameters indicate that the dose adjustment should be considered in male and female.