RESUMEN
Objectives To build a lamotrigine (LTG) physiologically based pharmacokinetic (PBPK) model (LTG PBPK) and compare it to the clinical data from South Asian Indian patients and use this model to understand the drug interactions of LTG and explore the optimal doses. Methods and Material The PBPK model was developed using the PK-Sim software platform and qualified with LTG plasma concentration data from an Indian study. The European population database was chosen as the patient setting in the software. Physiochemical data of LTG and enzyme kinetic data were incorporated from the literature. Dosing protocols were as per the previous study. Interaction models for drug interactions with carbamazepine and valproate were also simulated. Results Most of the model predicted concentration-time profiles of LTG at steady-state were well within the observed concentrations. The developed models were suitably qualified. The drug interaction model was used to assess the impact of induction and inhibition of the pharmacokinetic profile of LTG. Conclusions The predicted plasma concentrations of the developed PBPK models using the European population database were very similar to the data from Indian patients. The developed LTG PBPK models are applicable in predicting the impact of drug interactions and can yield appropriate LTG doses to be administered.
RESUMEN
The aim of this review was to systematically explore the underlying musculoskeletal biomechanical mechanisms of carrying and to describe its potential relationship with low back pain. This literature review was carried out using AMED, CINAHL, Compendex and MEDLINE electronic databases. Articles published from 2004 to 2012 were selected for consideration. Articles were considered if at least one measurement of kinetics, kinematics or other related musculoskeletal parameters related to biomechanics were included within the study. After combining the main keywords, 677 papers were identified. However, only 10 studies met all the inclusion criteria. Age, body mass index, gender and level of physical activity were identified as the factors that may influence the biomechanics of carrying activity. Carrying a loaded backpack was reported leading to posterior pelvic tilt, reduced lumbar lordosis, but increased cervical lordosis, thoracic kyphosis and trunk forward lean. Furthermore, while carrying bilaterally, lumbo-pelvic coordination was also reported to be more in-phase, as well as reduced coordination variability in transverse plane. Future studies investigating the biomechanics of a standardized carrying activity for clinical test are recommended.