Drug interactions factors contribution

While defining the overall pharmacokinetic or pharmacodynamic basis of botanical-drug interactions may be relatively straightforward, attempts to explain the underlying mechanism of altered drug concentrations or to predict the magnitude and significance of the interaction is certainly not easy. There are several factors that contribute to this difficulty, and they are briefly discussed below. 

Which of the following are factors contributing to the difficulty in assessing drug interactions with herbal products ... 

A number of factors contribute to the occurrence of drug interactions the most important factors will be discussed. 

There are no good predictors of the occurrence of dysrhythmias, but there are several susceptibility factors (26 7), including a history of sustained tachydysrhythmias, poor left ventricular function, and myocardial ischemia. Potassium depletion and prolongation of the QT interval are particularly important, and these particularly predispose to polymorphous ventricular dysrhythmias (for example torsade de pointes). Altered metabolism of antidysrhjdhmic drugs (for example liver disease, polymorphic acetylation or hydroxylation, and drug interactions) can also contribute. 

In this way, a predictive model is developed for pharmacokinetic parameters of individuals within the population. Compared with the traditional approach, there is some important additional information that can be obtained from this technique. Firstly, the factors contributing to pharmacokinetic variability in the target population can be identified and quantitated. Secondly, the eflFects of many variables can be screened, in fact as many variables as are collected on the case report form. This may enable identification of important drug interactions, or of other patient factors affecting pharmacokinetics that may not have been suspected. Thirdly, as efficacy and tolerability data have been collected in the same patients, this analysis might help to establish a range for therapeutic concentrations. 

The biochemical systems encountered by a drug molecule are extremely complex. Therefore, it should not be surprising that the factors affecting the drug s interactions and contributing to its final effect are also manyfold. The factors may be divided into three categories ... 

Funk C, Ponelle C, Scheuermann G, Pantze M (2001) Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat. Mot Pharmacol 59 627-635 Gale FA (2001) Lessons from the glitazones a story of drug development Lancet 357 1870-1875... 

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