Objective: This study was conducted to determine the efficacy of Snake anti-venom Immunoglobulin ... more Objective: This study was conducted to determine the efficacy of Snake anti-venom Immunoglobulin [IgG] manufactured by Anti-Snake Venom [ASV]/Anti-Rabies [ARV] Serology Laboratory, Health Department, Government of Sindh. Methods: The prospective, observational single arm study was conducted after the approval of IRB. Study included six patients with viper [Echis carinatus sochureki] snakebites referred to the emergency ward of Peoples University of Medical & Health Sciences Hospital, Nawabshah and District Headquarter Hospital Mithi, Sindh, Pakistan with consultation of Clinical and Principal investigator. The study was conducted over a period of three months [August 2015 to November 2015]. All patients were given IV infusion of 10 mL [1 vial] investigational ASV diluted in 100 mL normal saline except one patient who received 5 mL management dose and 5 mL subsequent dose for the recovery of coagulopathy. The efficacy was assessed by Primary and secondary efficacy endpoints, i.e. the...
Background Escitalopram is widely used for the management of the major depressive disorder and ge... more Background Escitalopram is widely used for the management of the major depressive disorder and generalized anxiety disorder, but there is no to very limited data available regarding efficacy and safety in Pakistani patients. This study was conducted to evaluate the efficacy and safety of escitalopram oral drops to manage the major depressive disorder and generalized anxiety disorder in a local cluster within Pakistan.MethodsThis prospective multicenter observational study was conducted in the department of psychiatry from August 2018 - August 2019. Eighty-five patients meeting the selection criteria were included in the study. Adolescent, adult, and geriatric patients of either gender with generalized anxiety disorder having Hamilton Anxiety Rating Scale (HAM-A) rate ≥ 10 and major depressive disorder having Montgomery-Asberg Depression Rating Scale (MADRS) rate ≥ 7 or patients with co-morbid generalized anxiety disorder (GAD), major depressive disorder (MDD) were selected for the study. We are reporting patients’ improvement from baseline, response rate, and remission rate. Data analysis is performed by using SPSS version 21 (IBM Inc, Armonk, USA).ResultsAmong enrolled patients, 42 were adolescents, 22 were adults, and 21 were geriatric. The mean age of an adolescent, adult, and geriatric patients was 14.92 ± 2.04, 44.54 ± 12.08, and 64.61 ± 3.16 years, respectively. Among enrolled patients, the mean change in a total score of HAM-A for anxiety and MADRS for depression were -10.04 ± 4.32 and -17.67 ± 14.42, respectively. At the end of the study, the remission rate and response rate for depression were 82 % and 75%, respectively. Similarly, the remission rate and the response for anxiety were 76% and 81%, respectively. Mean HAM-A and MADRS scores were significantly improved for adolescent, adult, and geriatric patients. Adverse events were reported in eight (9.41%) patients with six having gastrointestinal (GI) disturbance and two having to worsen anxiety. All reported adverse events were of mild severity. Conclusion Escitalopram oral drops are found effective and tolerable in reducing both anxiety and depression over the duration of study in all age groups, including adolescents, adults, and geriatrics.
BackgroundIn Pakistan, there is a paucity of published clinical data regarding the efficacy of so... more BackgroundIn Pakistan, there is a paucity of published clinical data regarding the efficacy of sofosbuvir-velpatasvir in the management of patients with hepatitis C without cirrhosis or with compensated cirrhosis.MethodsA prospective, open-label, multicenter, interventional trial was conducted in patients with hepatitis C without cirrhosis or with compensated cirrhosis. Hepatitis C patients without cirrhosis or with compensated cirrhosis were screened, and 133 patients were enrolled in the study. They received sofosbuvir 400 mg plus velpatasvir 100 mg combination once daily for 12 weeks. Patients were followed up for six months after the start of therapy. Hepatitis C viral load was assessed at baseline, at week 12, and after 24 weeks following the start of the treatment. The trial was prospectively registered with the Iranian Registry of Clinical Trials (IRCT) with the identification number IRCT20170614034526N4.ResultsAmong enrolled patients, 79 were male, and 54 were female. Ninety-five (71.4%) patients were without cirrhosis, and 38 had compensated cirrhosis. Patients without cirrhosis had a mean age of 45.90 ±10.99 years, and patients with compensated cirrhosis had a mean age of 52.60 ±12.29 years. As per the intention-to-treat analysis, all patients without cirrhosis and 35 (92.1%) patients with compensated cirrhosis achieved undetectable viral load hepatitis C virus (HCV) ribonucleic acid (RNA) of <15 IU/mL at 12 weeks from the start of treatment. Eighty-six (90.5%) patients without cirrhosis achieved sustained virologic response 12 weeks after the end of therapy. Patients with compensated cirrhosis experienced more adverse events (31.5%) than patients without cirrhosis (20.15%).ConclusionDirect-acting antiviral therapy using sofosbuvir and velpatasvir combination is effective and safe in HCV patients without cirrhosis and patients with compensated cirrhosis.
The objective of this study was to evaluate the predictive performances of allometric models and ... more The objective of this study was to evaluate the predictive performances of allometric models and a physiologically based pharmacokinetic model (PBPK) to predict clearance of glucuronidated drugs in neonates (3 months of age). From the literature, clearance values for 9 drugs (glucuronidated) for neonates and adults were obtained. Three allometric models were used to predict clearances of these glucuronidated drugs. A PBPK model was developed using the physicochemical, biopharmaceutical, and metabolic properties together with known pediatric physiology and enzymatic ontogeny. The model was first developed for adult subjects and then verified using external data and then applied to simulations in neonates. The predictive performances of allometric and PBPK models were evaluated by comparing the predicted values of clearance with the observed clearance values in the neonates. For 9 drugs, there were 13 age groups (preterm and term neonates) for which prediction error in mean clearance values within 0.5-to 1.5-fold was observed in 10 and 11 age groups by 2 allometric models and a PBPK model, respectively. The proposed allometric methods can predict mean clearances of glucuronidated drugs in preterm and term neonates (3 months of age) with reasonable accuracy (within 0.5-to 1.5-fold or 50% error) and are of practical value during neonatal drug development. The predicted mean clearance values of glucuronidated drugs in neonates 3 months of age by 2 allometric methods were comparable with the PBPK model.
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treat... more Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application. Mainly metabolized by hepatic route, and excreted through biliary tract, this dug has been found to possess high variation in patients in its pharmacokinetic (PK) profile. Physiologically based pharmacokinetic (PBPK) models using compartmental approach have attained their position to foresee the possible PK behavior of different drugs before their administration to patients and such models have been proposed for several anticancer agents. In this work, we used WB-PBPK technology to develop a model in a population of tumor patients who used IV irinotecan therapy. This model depicted the concentration of drug and its pharmacologically active metabolite in human body over a specific period of time. Knowledge about pharmacokinetic parameters is extracted from this profile and the model is evaluated by the observed results of clinical study presented in literature. The predicted behavior of the drug by this approach is in good agreement with the observed results and can aid in further exploration of PK of irinotecan in cancer patients, especially in those concomitantly suffer from other morbidity.
Objectives: To measure awareness about adverse drug reaction (ADRs) reporting among doctors, phar... more Objectives: To measure awareness about adverse drug reaction (ADRs) reporting among doctors, pharmacists and nurses and to determine reasons of ADRs under‑reporting in Pakistan. Methods: In present study, a self‑administered questionnaire was used to measure the awareness level about ADRs reporting among health care professionals (HCPs) of Pakistan. This was a cross sectional study. Results: Out of the respondents 51 % were physicians, 29.7 % pharmacists and 19.3 % were nurses. 65.5 % of HCP population observed ADRs, out of which only 57.4 % reported these in their respective hospitals. About 77.3 % of population understood the importance of reporting ADRs while 67.3 % of population agrees that pharmacists are chief personnel for the development of system. 71.8 % of HCPs agrees that ADRs are not reported because Commu‑ nity pharmacy lacks legally qualified pharmacists. Only 14.3 % of HCPs population knows that there is any ADR report‑ ing organization in Pakistan. Conclusion: The study recommends the need of such reporting system and more than half of the studied popula‑ tion agreed that pharmacists are required in developing such system.
Objective: This study was conducted to determine the efficacy of Snake anti-venom Immunoglobulin ... more Objective: This study was conducted to determine the efficacy of Snake anti-venom Immunoglobulin [IgG] manufactured by Anti-Snake Venom [ASV]/Anti-Rabies [ARV] Serology Laboratory, Health Department, Government of Sindh. Methods: The prospective, observational single arm study was conducted after the approval of IRB. Study included six patients with viper [Echis carinatus sochureki] snakebites referred to the emergency ward of Peoples University of Medical & Health Sciences Hospital, Nawabshah and District Headquarter Hospital Mithi, Sindh, Pakistan with consultation of Clinical and Principal investigator. The study was conducted over a period of three months [August 2015 to November 2015]. All patients were given IV infusion of 10 mL [1 vial] investigational ASV diluted in 100 mL normal saline except one patient who received 5 mL management dose and 5 mL subsequent dose for the recovery of coagulopathy. The efficacy was assessed by Primary and secondary efficacy endpoints, i.e. the...
Background Escitalopram is widely used for the management of the major depressive disorder and ge... more Background Escitalopram is widely used for the management of the major depressive disorder and generalized anxiety disorder, but there is no to very limited data available regarding efficacy and safety in Pakistani patients. This study was conducted to evaluate the efficacy and safety of escitalopram oral drops to manage the major depressive disorder and generalized anxiety disorder in a local cluster within Pakistan.MethodsThis prospective multicenter observational study was conducted in the department of psychiatry from August 2018 - August 2019. Eighty-five patients meeting the selection criteria were included in the study. Adolescent, adult, and geriatric patients of either gender with generalized anxiety disorder having Hamilton Anxiety Rating Scale (HAM-A) rate ≥ 10 and major depressive disorder having Montgomery-Asberg Depression Rating Scale (MADRS) rate ≥ 7 or patients with co-morbid generalized anxiety disorder (GAD), major depressive disorder (MDD) were selected for the study. We are reporting patients’ improvement from baseline, response rate, and remission rate. Data analysis is performed by using SPSS version 21 (IBM Inc, Armonk, USA).ResultsAmong enrolled patients, 42 were adolescents, 22 were adults, and 21 were geriatric. The mean age of an adolescent, adult, and geriatric patients was 14.92 ± 2.04, 44.54 ± 12.08, and 64.61 ± 3.16 years, respectively. Among enrolled patients, the mean change in a total score of HAM-A for anxiety and MADRS for depression were -10.04 ± 4.32 and -17.67 ± 14.42, respectively. At the end of the study, the remission rate and response rate for depression were 82 % and 75%, respectively. Similarly, the remission rate and the response for anxiety were 76% and 81%, respectively. Mean HAM-A and MADRS scores were significantly improved for adolescent, adult, and geriatric patients. Adverse events were reported in eight (9.41%) patients with six having gastrointestinal (GI) disturbance and two having to worsen anxiety. All reported adverse events were of mild severity. Conclusion Escitalopram oral drops are found effective and tolerable in reducing both anxiety and depression over the duration of study in all age groups, including adolescents, adults, and geriatrics.
BackgroundIn Pakistan, there is a paucity of published clinical data regarding the efficacy of so... more BackgroundIn Pakistan, there is a paucity of published clinical data regarding the efficacy of sofosbuvir-velpatasvir in the management of patients with hepatitis C without cirrhosis or with compensated cirrhosis.MethodsA prospective, open-label, multicenter, interventional trial was conducted in patients with hepatitis C without cirrhosis or with compensated cirrhosis. Hepatitis C patients without cirrhosis or with compensated cirrhosis were screened, and 133 patients were enrolled in the study. They received sofosbuvir 400 mg plus velpatasvir 100 mg combination once daily for 12 weeks. Patients were followed up for six months after the start of therapy. Hepatitis C viral load was assessed at baseline, at week 12, and after 24 weeks following the start of the treatment. The trial was prospectively registered with the Iranian Registry of Clinical Trials (IRCT) with the identification number IRCT20170614034526N4.ResultsAmong enrolled patients, 79 were male, and 54 were female. Ninety-five (71.4%) patients were without cirrhosis, and 38 had compensated cirrhosis. Patients without cirrhosis had a mean age of 45.90 ±10.99 years, and patients with compensated cirrhosis had a mean age of 52.60 ±12.29 years. As per the intention-to-treat analysis, all patients without cirrhosis and 35 (92.1%) patients with compensated cirrhosis achieved undetectable viral load hepatitis C virus (HCV) ribonucleic acid (RNA) of <15 IU/mL at 12 weeks from the start of treatment. Eighty-six (90.5%) patients without cirrhosis achieved sustained virologic response 12 weeks after the end of therapy. Patients with compensated cirrhosis experienced more adverse events (31.5%) than patients without cirrhosis (20.15%).ConclusionDirect-acting antiviral therapy using sofosbuvir and velpatasvir combination is effective and safe in HCV patients without cirrhosis and patients with compensated cirrhosis.
The objective of this study was to evaluate the predictive performances of allometric models and ... more The objective of this study was to evaluate the predictive performances of allometric models and a physiologically based pharmacokinetic model (PBPK) to predict clearance of glucuronidated drugs in neonates (3 months of age). From the literature, clearance values for 9 drugs (glucuronidated) for neonates and adults were obtained. Three allometric models were used to predict clearances of these glucuronidated drugs. A PBPK model was developed using the physicochemical, biopharmaceutical, and metabolic properties together with known pediatric physiology and enzymatic ontogeny. The model was first developed for adult subjects and then verified using external data and then applied to simulations in neonates. The predictive performances of allometric and PBPK models were evaluated by comparing the predicted values of clearance with the observed clearance values in the neonates. For 9 drugs, there were 13 age groups (preterm and term neonates) for which prediction error in mean clearance values within 0.5-to 1.5-fold was observed in 10 and 11 age groups by 2 allometric models and a PBPK model, respectively. The proposed allometric methods can predict mean clearances of glucuronidated drugs in preterm and term neonates (3 months of age) with reasonable accuracy (within 0.5-to 1.5-fold or 50% error) and are of practical value during neonatal drug development. The predicted mean clearance values of glucuronidated drugs in neonates 3 months of age by 2 allometric methods were comparable with the PBPK model.
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treat... more Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application. Mainly metabolized by hepatic route, and excreted through biliary tract, this dug has been found to possess high variation in patients in its pharmacokinetic (PK) profile. Physiologically based pharmacokinetic (PBPK) models using compartmental approach have attained their position to foresee the possible PK behavior of different drugs before their administration to patients and such models have been proposed for several anticancer agents. In this work, we used WB-PBPK technology to develop a model in a population of tumor patients who used IV irinotecan therapy. This model depicted the concentration of drug and its pharmacologically active metabolite in human body over a specific period of time. Knowledge about pharmacokinetic parameters is extracted from this profile and the model is evaluated by the observed results of clinical study presented in literature. The predicted behavior of the drug by this approach is in good agreement with the observed results and can aid in further exploration of PK of irinotecan in cancer patients, especially in those concomitantly suffer from other morbidity.
Objectives: To measure awareness about adverse drug reaction (ADRs) reporting among doctors, phar... more Objectives: To measure awareness about adverse drug reaction (ADRs) reporting among doctors, pharmacists and nurses and to determine reasons of ADRs under‑reporting in Pakistan. Methods: In present study, a self‑administered questionnaire was used to measure the awareness level about ADRs reporting among health care professionals (HCPs) of Pakistan. This was a cross sectional study. Results: Out of the respondents 51 % were physicians, 29.7 % pharmacists and 19.3 % were nurses. 65.5 % of HCP population observed ADRs, out of which only 57.4 % reported these in their respective hospitals. About 77.3 % of population understood the importance of reporting ADRs while 67.3 % of population agrees that pharmacists are chief personnel for the development of system. 71.8 % of HCPs agrees that ADRs are not reported because Commu‑ nity pharmacy lacks legally qualified pharmacists. Only 14.3 % of HCPs population knows that there is any ADR report‑ ing organization in Pakistan. Conclusion: The study recommends the need of such reporting system and more than half of the studied popula‑ tion agreed that pharmacists are required in developing such system.
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