Pharmacotherapy, in many cases, is practiced at a suboptimal level of performance in low- and middle-income countries (LMICs) although stupendous amounts of data are available regularly. The process of drug development is time-consuming, costly, and is also associated with loads of hurdles related to the safety concerns of the compounds. This review was conducted with the objective to emphasize the role of pharmacometrics in pharmacotherapy and the drug development process in LMICs for rational drug therapy. Pharmacometrics is widely applied for the rational clinical pharmacokinetic (PK) practice through the population pharmacokinetic (popPK) modeling and physiologically based pharmacokinetic (PBPK) modeling approach. The scope of pharmacometrics practice is getting wider day by day with the untiring efforts of pharmacometricians. The basis for pharmacometrics analysis is the computer-based modeling and simulation of pharmacokinetics/pharmacodynamics (PK/PD) data supplemented by characterization of important aspects of drug safety and efficacy. Pharmacometrics can be considered an invaluable tool not only for new drug development with maximum safety and efficacy but also for dose optimization in clinical settings. Due to the convenience of using sparse and routine patient data, a significant advantage exists in this regard for LMICs which would otherwise lag behind in clinical trials.

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.

Gelatin-based hydrogels have shown good injectability and biocompatibility and have been broadly used for drug delivery and tissue regeneration. However, their low mechanical strengths and fast degradation rates must be modified for long-term implantation applications. With an aim to develop mechanically stable hydrogels, reactive anhydride-based oligomers were developed and used to fabricate gelatin-based crosslinked hydrogels in this study. A cascade of hydrophilic oligomers containing reactive anhydride groups was synthesized by free radical polymerization. These oligomers varied in degree of reactivity, comonomer composition, and showed low molecular weights (M_n < 5 kDa). The reactive oligomers were utilized to fabricate hydrogels that differed in their mechanical strengths and degradation profiles. These formulations exhibited good cytocompatibility with human adipose tissue-derived stem cells (hADCs). In conclusion, the reactive MA-containing oligomers were successfully synthesized and utilized for the development of oligomer-crosslinked hydrogels. Such oligomer-crosslinked gelatin-based hydrogels hold promise as drug or cell carriers in various biomedical applications.

A fully validated bioanalytical methods are prerequisite for pharmacokinetic and bioequivalence studies as well as for therapeutic drug monitoring. Due to high pharmacokinetic variability and narro...

Purpose: The pharmacokinetics of voriconazole have been studied across various populations but data specific to the Pakistani cancer population has not yet been reported. The aim of present study was to explore and identify covariates that affect pharmacokinetics of intravenous voriconazole in Pakistani cancer population. Methods: The therapeutic drug monitoring data from January1^st, 2023 to December 31^st, 2023 of cancer patients receiving intravenous voriconazole for systemic fungal infections were taken from electronic medical record of the hospital. The data were used for the development of population pharmacokinetic model using NONMEM. Impact of various covariates such as age, weight, sex, liver function test, serum creatinine, creatinine clearance, type of cancer (primary diagnosis) and type of fungal infection were assessed through stepwise covariate modeling. Bootstrap analysis and goodness of fit plots were used to evaluate robustness and predictive performance of final model. Results: One compartment model best described the included data with first order elimination. The value of voriconazole clearance was 6.17 L/h with interindividual variability of 83.7% while volume of distribution was 55.9 L. The clearance of voriconazole was significantly influenced by renal status of patients. Creatinine clearance and primary diagnosis were significant covariates affecting clearance of voriconazole in covariate analysis. Conclusion: The findings suggest that this model can be used for dosage adjustment based on creatinine clearance and primary diagnosis as they impact significantly on voriconazole clearance in cancer patients. This approach is especially valuable in resource-limited settings like Pakistan, where individualized therapy can enhance the safety and efficacy of antifungal treatment, addressing the unique clinical and demographic challenges in vulnerable populations.

Background COVID-19 pandemic has portentously frightened the existence of life all over the world. The lockdown approach was adopted as a containment strategy as the disease itself has manifested severe social, economic, and psychiatric implications. Objectives To explore the perception and preparedness of international medical students residing in university hostels amid the COVID-19 pandemic lockdown. Design A semi-structured interview guide was developed in this qualitative study design. All the interviews were audio-taped, transcribed verbatim, and then analyzed for thematic contents by standard content analysis framework. Setting Interviews were conducted in university hostels in Punjab, Pakistan. Participants A total of 11 international medical students were interviewed face-to-face through the purposive sampling technique to obtain in-depth individual viewpoints. Results The thematic content analysis yielded five major themes: Familiarity with COVID-19, Perceptions and attitudes towards COVID-19, Preparedness for safety against COVID-19, Barriers to lifestyle, and Psychological perspectives. A better general perception and preparedness among international medical students regarding COVID-19 was found. Good knowledge regarding the overview of COVID-19; adequate preventive approaches such as social distancing, use of masks, gloves, and sanitizers; and compliance with the lockdown measures were reported by the respondents. The pertinent issue raised by the respondents is the disturbance in normal routine due to distortion in social life and isolation that may cause psychological stress. Conclusions The findings from this study lighten the people’s perspectives that help the government to prepare public health strategies based on population-focused approaches. The present study demonstrates the respondents’ opinion on COVID-19 management by personal hygiene, social distancing, and complying with the lockdown measures. Furthermore, it demands that timely and evidence-based teaching-learning techniques should be adopted for students’ engagement which ensures mental health and self-motivation as well. Therefore, they can utilize their time productively which could have a long-term effect on their careers and healthcare services.