Systemic circulation, drug concentration profiles

Fig. 1 Drug concentration profiles in the systemic circulation as a result of taking a series of multiple doses of a conventional drug-delivery system (Ai, A2,. ..) in comparison with the ideal drug concentration profile (B). (Adapted from...

The total radioactivity minus the parent compound concentration (determined by the bioanalytical method) in a specimen estimates the amount of metabolites present. If the difference is minimal and does not change over time, the extent of metabolism is low. For plasma or serum specimens, a small difference indicates that metabolites are not present in systemic circulation. For bile or urine specimens, high levels of radioactivity suggest a primary route of elimination for the parent and metabolites. For a drug candidate cleared primarily by metabolism, a preliminary metabolite profile in urine and bile can determine the number of potential metabolites. When the level of a metabolite in a matrix is high, attempts to isolate and identify the metabolite can be undertaken. If sufficient quantities are obtained, the metabolite s pharmacologic and toxicologic... 

The pharmacologic activity profile of a systemically active drug is a function of its intrinsic activity and of the concentration profile that is achieved in the circulation. The speed of onset of action and the intensity... 

Equation 12.3 may be employed to predict the plasma concentration of drug at any time during the dosing interval following the administration of nth dose (second, third, fourth, etc) (Fig. 12.2). However, in order to make such predictions, it is essential to have knowledge of the apparent volume of distribution, the fraction of the administered dose absorbed into the systemic circulation, the apparent first-order rate constant for absorption, the intercept of the plasma concentration versus time profile following the administration of the single dose, and the elimination rate constant. Furthermore, earlier... 

The area under the plasma concentration-time curve is a useful indicator of the amount of drug that reaches the systemic circulation and of the duration resides there before it is removed. The processes of ADME influence the plasma concentration-time profile of an administered drug and the associated parameters. For example, a reduction in the rate of elimination of nifedipine will result in elevated and prolonged drug levels in plasma (Figure 5). 

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