Background. Isoniazid (INH) is one of the drugs in the classical therapy for pulmonary tuberculosis. Several INH population pharmacokinetic models were established in the last ten years. This systemic review was performed i) to summarize published population pharmacokinetic (PPK) models of INH and ii) to summarize and explore identified covariates influencing the INH pharmacokinetic models. Methods. A search of publication for population pharmacokinetic analyses of INH either in healthy volunteers or patients from 2011 to 2021 was conducted in PubMed databases. Reviews, methodology articles, non-compartmental analysis, in-vitro, and animal studies, were excluded. Results. 12 studies were included in this review. INH pharmacokinetics was described as two-compartment with first-order absorption and elimination in most of the included studies. In most of the studies, N-acetyltransferase 2 (NAT2 ) genotype polymorphism (n=11) was the most common identified covariates affecting INH pharmacokinetic parameters. Body weight (n=2) and body mass index (BMI) (n=1) were the most common significant covariates retained in the final model. Conclusions . The population pharmacokinetic of INH has been extensively reviewed and the published PPK models of INH and its parameters were summarized in this review. The PPK variability of INH was reported to be explained mainly by the NAT2 genotype polymorphism on the clearance (CL) parameter. This review shows that to optimise and rationalise the dosing regimen of INH, a patient’s NAT2 genotype should be considered. Body weight and BMI value should be taken into consideration when making dosing adjustments for INH to achieve therapeutic range.

The link between COPD and osteoporosis is unclear and yet to be understood. This study aimed at detecting the prevalence and investigate the predictors for low bone mineral density among COPD patients and tested a new risk assessment tool for the early screening of osteoporosis among COPD patients.This study is a longitudinal observational study conducted from June-2019 until December-2020 at a tertiary care setting in Penang, Malaysia. Follow-ups were arranged every six months. During the study, patients’ BMD was checked every visit, and the subjects’ pulmonary parameters were recorded, including; mMRC dyspnea scores, CAT scores, spirometry results, exacerbations history, and SpO2%. Furthermore, a novel risk assessment tool was validated in this study, and logistic regression was conducted to find low BMD predictors among COPD patients. Based on T-score, more than 50% of subjects were osteoporotic based. The overall mean±SD for patients’ age was 65.4±10.04. The overall mean±SD for patients’ BMI was 23.32±5.43. Both FEV1% predicted, and FEV/FVC was significantly lower among osteoporotic subjects, and lower mMRC stages were observed among non-osteoporotic patients. For the novel risk assessment tool, a cutoff point of 34 made the optimum balance between sensitivity and specificity (0.867 and 0.087, respectively) with an AUC of 0.934. Furthermore, severe COPD patients were four times at higher risk of getting osteoporosis, FEV% predicted, and FEV/FVC was inversely related to the risk of osteoporosis. Patients with severe dyspnea had twice the risk of getting osteoporosis.Osteoporosis was prevalent among COPD patients. For a screening tool, the risk assessment tool showed good sensitivity and precision in detecting osteoporotic subjects among COPD patients. Severe COPD patients were significantly at higher risk of getting osteoporosis.