Drug quantitative prediction

Erhardt PW. A human drug metabolism database potential roles in the quantitative predictions of drug metabolism and metabolism-related drug-drug interactions. Curr Drug Metab 2003 4 411-22. 

Chong, S., S. A. Dando, K. M. Soucek, and R. A. Morrison. In vitro permeability through caco-2 cells is not quantitatively predictive of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system, Pharm. Res. 1996, 13, 120-123... 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

Quantitative Prediction of Drug-Drug Interaction Caused by Irreversible CYP Inhibitors... 

To make quantitative predictions of DDI for the new compound as perpetrator, a reliable estimate of a relevant in vivo concentration is needed. What is tmly needed is knowledge of the concentration of the inhibitor available to bind to the enzyme. For liver, if the well accepted free-dmg hypothesis (which underwrites fundamental drug action principles in pharmacology) is applied for DDI, then the use of a free intracellular liver concentration is needed. For inhibitors that are permeable through membranes, the free concentration in the portal vein should serve as the closest proxy for free intracellular concentration in the liver. Diminished permeability as well as active uptake and efflux from liver cells can confound this relationship. Nevertheless, use of estimates of unbound portal vein concentrations (which can be estimated from... 

Obach, R.S., Walsky, R.L, Venkatakrishnan, K., Houston, J.B. and Tremaine, L.M. (2005) vitro cytochrome P450 inhibition data and the prediction of drug-drug interactions qualitative relationships, quantitative predictions, and the rank-order approach. Clinical Pharmacology and Therapeutics, 78, 582-592. 

Kanamitsu, S., Ito, K. and Sugiyama, Y. (2000) Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics use of maximum unbound concentration of inhibitor at the inlet to the liver. Pharmaceutical Research,... 

The experimentally derived empirical expressions used in models such as the mass-action framework have contributed greatly to the logical selection of surfactants for efLcient and effective solubilization of drugs. However, there is currently a need to develop more efLcient, less toxic surfactants for use in drug delivery. A model that is able to provide quantitative prediction of the critical micelle concentration and micelle size without the need for extensive experimental measurements would greatly accelerate the development of novel surfactant chemistries for use in pharmaceutical applications. 

De Graaf IAM, Van Meijern CE, Pektas F, Foster HJ (2002) Comparison of in Vitro Preparations for Semi-Quantitative Prediction of in Vivo Drug Metabolism. Drug Metab Dis-pos 30 1129-1136... 

Ito K, Iwatsubo T, Kanamitsu S, Nakajima Y, Sugiyama Y. Quantitative prediction of in vivo drug clearance and drug interactions from in vitro data on metabolism, together with binding and transport. Annu Rev Pharmacol Toxicol 1998 38 461-99. 

Assessment of percutaneous absorption for any topically applied drug or chemical, can be classified based either on a model s level of biological complexity (in silico, in vitro, in vivo) or on the specific species studied (human, laboratory rodent, monkey, pig). The goal of the research should also be taken into consideration. Is the work being conducted to study the mechanism of absorption (e.g., identify a specific mathematical model or assess the effect of a vehicle) or to quantitatively predict absorption in humans Is the study designed to look at a local effect in skin or a systemic effect after absorption That is, are skin concentrations the relevant metric or is flux of chemical across skin important Model systems and approaches in use today to assess dermal absorption have recently been extensively reviewed [1]. 

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