The application of in silico methods for predicting internal dosimetry of a compound has gained attention in the past few years from academia, government and industry. One such method based on both compound- and organism-specific information is physiologically-based pharmacokinetic (PBPK) modeling. Numerous promises surrounding the potential of PBPK models to guide drug development (DD) and human health risk assessment (HHRA) have been made with primary areas of application being incorporation of in vitro data for pharmacokinetic prediction in early drug development, interspecies scaling, intra-human scaling and, of special interest, prediction of drug-drug interaction potential. This article addresses the question 'Have physiologically-based pharmacokinetic models delivered?' through analysis of its promises and accomplishments in real-world situations. Progress on PBPK model use in DD and HHRA has been demonstrated, especially in the area of interspecies and adult-to-children scaling, although its actual application is not reflected in the number of published works. Future advances will depend on continued model development as well as integration of PBPK models with models of response and/or disease. More importantly, increased training along with managerial and regulatory support is imperative to the continued integration of PBPK modeling in both HHRA and DD.
Two basic mechanisms which operate in the functioning of reactive armour are presented. Both the explosive effect and cutting of metal plates by a jet have been investigated. The angle of attack and the confinement of the explosive have been found most significant factors in reducing the penetrating power of the jet. The effect of detonating explosives has been investigated with radiography. Some of the significant effects, like detonation of explosive by the impact of the jet, expansion of covering plates, disturbance in coherence and reduction in the penetration of the jet have been observed. It is found that the jet penetration in a stack of mild steel plates is reduced to 30 per cent of its blank penetration in present set-ups. A theoretical model has been conceived to study the interaction of moving plates and the jet. The critical thickness and surface cut in plates have been calculated.
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