METHODS: The MEDLINE and EMBASE databases, as well as the reference lists of all articles, were searched to identify population PK models of tacrolimus developed from adult transplant recipients published from the inception of the databases to 29 February 2020.
RESULTS: Of the 69 studies identified, 55% were developed from kidney transplant recipients and 30% from liver transplant recipients. Most studies (91%) investigated the oral immediate-release formulation of tacrolimus. Few studies (17%) explained the effect of drug-drug interactions on tacrolimus PK. Only 35% of the studies performed an external evaluation to assess the generalizability of the models. Studies related variability in tacrolimus whole blood clearance among transplant recipients to either cytochrome P450 (CYP) 3A5 genotype (41%), days post-transplant (30%), or hematocrit (29%). Variability in the central volume of distribution was mainly explained by body weight (20% of studies).
CONCLUSION: The effect of clinically significant drug-drug interactions and different formulations and brands of tacrolimus should be considered for any future tacrolimus population PK model development. Further work is required to assess the generalizability of existing models and identify key factors that influence both initial and maintenance doses of tacrolimus, particularly in heart and lung transplant recipients.
METHOD: This paper aims to develop a sustainable pedestrian gap crossing index model based on traffic flow density. It focusses on the gaps accepted by pedestrians and their decision for street crossing, where (Log-Gap) logarithm of accepted gaps was used to optimize the result of a model for gap crossing behavior. Through a review of extant literature, 15 influential variables were extracted for further empirical analysis. Subsequently, data from the observation at an uncontrolled mid-block in Jalan Ampang in Kuala Lumpur, Malaysia was gathered and Multiple Linear Regression (MLR) and Binary Logit Model (BLM) techniques were employed to analyze the results.
RESULTS AND CONCLUSIONS: From the results, different pedestrian behavioral characteristics were considered for a minimum gap size model, out of which only a few (four) variables could explain the pedestrian road crossing behavior while the remaining variables have an insignificant effect. Among the different variables, age, rolling gap, vehicle type, and crossing were the most influential variables. The study concludes that pedestrians' decision to cross the street depends on the pedestrian age, rolling gap, vehicle type, and size of traffic gap before crossing.
PRACTICAL APPLICATIONS: The inferences from these models will be useful to increase pedestrian safety and performance evaluation of uncontrolled midblock road crossings in developing countries.