Drug disposition elimination

Polarized tissues directly involved in drug absorption (intestine) or excretion (liver and kidney) and restricted drug disposition (blood-tissue barriers) asymmetrically express a variety of different drug transporters in the apical or basolateral membrane resulting in vectorial dmg transport. This vectorial dmg transport is characterized by two transport processes the uptake into the cell and subsequently the directed elimination out of the cell (Figure 15.3). Because the uptake of substances... 

Wu C-Y, Benet LZ (2005) Predicting Drug Disposition via Application of BCS Transport/Absorption/Elimination Interplay and Development of a Biopharmaceu-tics Drug Disposition Classification System. Pharm. Res. 22 11-23... 

Wu, C.Z. and Benet, L.Z. (2005) Predicting drug disposition via application of BCS transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharmaceutical Research, 22, 11-23. 

At birth, term infants can metabolize and eliminate drugs. For most patients these systems did not function during fetal life and therefore even at birth are not very efficient. Table 6.1 outlines the time required for maturation of some of the systems used in drug absorption and elimination. Table 6.2 lists other factors that alter drug disposition in newborns. The ability to absorb and eliminate drugs increases slowly over the first month of life. 

Target-mediated drug disposition is often associated with nonlinearity in the pharmacokinetics of the affected drug, as the elimination pathway mediated via... 

In pharmaceutical research and drug development, noncompartmental analysis is normally the first and standard approach used to analyze pharmacokinetic data. The aim is to characterize the disposition of the drug in each individual, based on available concentration-time data. The assessment of pharmacokinetic parameters relies on a minimum set of assumptions, namely that drug elimination occurs exclusively from the sampling compartment, and that the drug follows linear pharmacokinetics that is, drug disposition is characterized by first-order processes (see Chapter 7). Calculations of pharmacokinetic parameters with this approach are usually based on statistical moments, namely the area under the concentration-time profile (area under the zero moment curve, AUC) and the area under the first moment curve (AUMC), as well as the terminal elimination rate constant (Xz) for extrapolation of AUC and AUMC beyond the measured data. Other pharmacokinetic parameters such as half-life (t1/2), clearance (CL), and volume of distribution (V) can then be derived. 

Traditionally, linear pharmacokinetic analysis has used the n-compartment mammillary model to define drug disposition as a sum of exponentials, with the number of compartments being elucidated by the number of exponential terms. More recently, noncompartmental analysis has eliminated the need for defining the rate constants for these exponential terms (except for the terminal rate constant, Xz, in instances when extrapolation is necessary), allowing the determination of clearance (CL) and volume of distribution at steady-state (Vss) based on geometrically estimated Area Under the Curves (AUCs) and Area Under the Moment Curves (AUMCs). Numerous papers and texts have discussed the values and limitations of each method of analysis, with most concluding the choice of method resides in the richness of the data set. 

Disposition in the Body. Readily absorbed after oral administration but extensively metabolised. Numerous metabolites, including traces of amphetamine, have been detected in the urine some unchanged drug is eliminated in the faeces. 

Hickey, A.J. Tian, Y. Parasrampuria, D. Kanke, M. Biliary elimination of bromsulfthalein, phenolphthalein, and doxorubicin released from microspheres following intravenous administration. Biopharm. Drug Disposition 1993, 14 (2), 181-186. 

To better understand changes in drug disposition, the pediatric population needs to be categorized into various groups (Table 1) because children vary markedly in their absorption, distribution, metabolism, and elimination of medications. This occurs because neonates, infants, children, adolescents, and adults have different body compositions (i.e., as to their percentages of body water and fat) and have their body organs in different stages of development. 

---