Objective: Digoxin, a cardiac glycoside with extensive clinical usage, poses challenges due to its narrow therapeutic index and wide interindividual variability. Population pharmacokinetic studies in healthy individuals are scarce despite their importance in understanding drug kinetics. This study aimed to characterize the population pharmacokinetics of oral digoxin in healthy volunteers. Methods: An open-label, single-dose pharmacokinetic study was conducted in 72 healthy Indian adults using digoxin tablets. Plasma samples were collected at various time points, and digoxin concentrations were quantified using Liquid Chromatography-Mass Spectrometry (LC-MS). Population pharmacokinetic analysis was performed using PUMAS® software, incorporating covariates such as creatinine clearance. Results: The two-compartment model best described the data, with a population estimate of clearance (CL/F) of 12.08 l/h in the base model and 8.3 l/h in the final model. Creatinine clearance significantly influenced digoxin clearance. Goodness-of-fit plots indicated model appropriateness, and Monte Carlo simulation validated model performance. Conclusion: This study presents a novel population pharmacokinetic model for oral digoxin in healthy individuals. The model accurately predicts digoxin pharmacokinetics and can guide dosage regimen optimization for better therapeutic outcomes. Further research should explore drug interactions and validate the model in diverse populations.

Warfarin is the most commonly prescribed anticoagulant medication. Warfarin's pharmacokinetics (PK) in its enantiomeric form have been reported to be highly variable. Five population pharmacokinetic model studies for warfarin were identified in this systematic review. This review summarized these studies and reported on various factors affecting warfarin PK. Most studies reported a one-compartment model with first-order absorption and elimination for both S-warfarin and R-warfarin. Warfarin disposition has been reported to be influenced by various factors, including gender, age, genetic variation, body surface area (BSA), concurrent drug, weight, and ethnicity. So, all of these factors must be considered when addressing this pharmacokinetic variability. These models should undergo an external evaluation to confirm their generalizability and to support model-informed dosing in clinical settings.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:The benefits of adverse drug reaction (ADR) monitoring are well-known. Poor awareness and nonavailability of a central co-ordinating body resulted in lack of ADR monitoring in India. The National Pharmacovigilance Programme was recently initiated, encouraging ADR monitoring in selected centres, including our centre.WHAT THIS STUDY ADDS:This is the first study of its kind at GHQH, Ootacamund that has provided insight into the burden of ADRs here. The incidence and severity of ADRs documented in our study is lower than those reported in comparable populations in Western studies but more than those reported in India.AIMS:To ascertain the current burden of ADRs at a Government hospital in Ooty and to assess the severity of reported ADRs and the additional financial burden associated with ADRs.METHODS:A prospective, spontaneous reporting study was conducted over a period of 9 months of inpatient admissions to the medical wards, co-ordinated by clinical pharmacists. The WHO definition of an ADR was adopted. The Naranjo algorithm scale was used for causality assessment. Confirmed ADRs were classified according to the Wills & Brown method and assessed for severity and patient outcomes. The average cost incurred in treating the ADRs was calculated.RESULTS:Of the total of 187 adverse drug events (ADEs) reported, 164 reports from 121 patients were confirmed as ADRs, giving an overall incidence of 9.8%. This included 58 (3.4%) ADR related admissions and 63 (3.7%) ADRs occurring during the hospital stay. About two thirds of the reactions (102, 62.2%) were classified as probable. The majority of the reactions (88, 53.7%) were mild. Most patients (119, 72.6%) recovered from the incidence. The majority of the reactions were of type H (100, 61%) which indicates that they were not predictable and not potentially preventable. An average cost of 481 rupees ( pound 6) was spent on each patient to manage ADRs.CONCLUSIONS:The incidence and severity of ADRs documented in our study are lower than those reported in comparable populations in Western studies but more than those reported in India.

A high performance liquid chromatographic method is described for estimation of glibenclamide in human serum. After precipitation with methanol, the separation of glibenclamide and internal standard was accomplished using reversed phase chromatography. The mobile phase, a combination of acetonitrile and 25 mM phosphate buffer (pH 3.5) at 3:2 ratio was run isocraticaly through a C18 analytical column. The UV detection was done at 253 nm for glibenclamide. Analytical run time was less than 12 min. Mean recovery was 92% for 0.5 µg/ml concentrations. The assay exhibited good linear relationship between peak area ratios and serum concentration. Quantification limit was at least 25 ng/ml of glibenclamide and accuracy and precision were over the concentration range of 50-500 ng/ml. Assay was successfully applied to the measurement of glibenclamide in serum for therapeutic drug monitoring.

A high performance liquid chromatographic method is described for simultaneous estimation of amiodarone and its metabolite desethylamiodarone in plasma. After precipitation with acetonitrile, the separation of amiodarone, desethylamiodarone and internal standard was accomplished using reversed phase chromatography. The mobile phase, a combination of ammonium acetate (pH 3.5 adjusted with ortho phosphoric acid) and acetonitrile was run isocratically through a C18 analytical column. The UV detection was done at 242 and 247 nm for amiodarone and desethylamiodarone respectively. Analytical run time was 10 min. Mean recovery was 84% for 0.5 µg/ml concentrations. The assay exhibited good linear relationship between peak height ratios and plasma concentration. Quantification limit was at least 0.01 µg/ml of amiodarone and desethylamiodarone. Accuracy and precision were over the concentration range of 0.01-10 µg/ml. Assay was successfully applied to the measurement of amiodarone and its metabolite desethylamiodarone in human plasma of patients who were on long-term oral therapy on amiodarone.

Digoxin is a widely used drug in patients with congestive heart failure. The present study compared the quality of life of congestive heart failure patients on one year follow-up period with two different dosing of digoxin (5/7 therapy and 7/7 therapy in whom the target serum digoxin concentration is maintained). Quality of life significantly improved in intervention group thus emphasizing the need for continuous dosing of digoxin based on target concentration.

BACKGROUND & OBJECTIVEAminoglycoside antibiotics, especially gentamicin, are widely used in suspected Gram-negative infections in India. Therapeutic drug monitoring is not commonly used for this drug in our population. We evaluated the target concentration intervention (TCI) strategy of gentamicin therapy in a predominantly malnourished patient population with lower respiratory tract infection in south India.METHODSPatients who were prescribed gentamicin for suspected lower respiratory tract infection were randomized to any of the three groups, viz., control (CG), once daily dosing (ODD), and pharmacokinetic dosing (TCI) groups. Diagnosis was initially done by clinical evaluation and confirmed radiologically. Patients in CG received 80 mg gentamycin twice daily, ODD group received 160 mg once daily, and TCI groups received 160 mg once daily initially followed by dose revision based on serum drug levels. Blood samples were collected at peak and trough levels and assayed for gentamicin concentration. Dose adjustment was done in TCI group whereas the other groups received standard doses. Efficacy and safety were evaluated as outcome measures.RESULTSOf the 52 patients included initially in the study, 43 (CG 20, ODD 12, TCI 11) completed the study. The doses administered to the study subjects were less than those prescribed in standard textbooks and guidelines. Patients in TCI group had their gentamicin doses revised upwardly to a dose of 4.3+/-0.6 mg/kg to achieve a peak gentamicin concentration of 12 to 15 microg/ml. Both ODD and TCI groups showed significant improvements in outcomes studied over the control group.INTERPRETATION & CONCLUSIONThe results of our study indicated that once daily dosing of gentamycin was superior to multiple daily dosing in treating the lower respiratory tract infection in the study population. All patients in the ODD and TCI groups achieved satisfactory serum drug concentrations at administered doses (160 mg/day for ODD and <or= 200 mg/day for TCI group). In our study, target concentration intervention did not significantly improve the therapy outcomes. Since the study sample is small further research may be needed.

The stability of liposomes after introduction into the body is presently being discussed and needs thorough understanding. Hence, as a nonliposomal approach, egg albumin nanospheres were prepared by the pH-coacervation method, and a preliminary study was carried out of the influence of process variables on the size and shape of nanospheres by changing the pH of the albumin solution, concentration of albumin solution, and volume of cross-linking agent. The batch prepared with an albumin medium of pH 9, 2% concentration, and 100 microliters of 4% glutaraldehyde-ethanol solution was found to have a spherical uniform shape with an average size of 497.6 nm. The ideal batch was loaded with the systemic antifungal drug amphotericin-B. Drug-loaded nanospheres were evaluated to study their in vitro release. They were found to exhibit a biphasic pattern with a cumulative percentage release of 97.7%.