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By Lullmann H.

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Tubular reabsorption pH = 7,0 pKa of substance pKa = 7,0 100 + R N H 50 Concentration of drug in tubule 1,2 l Final urine % R N 6 6,5 7 7,5 8 pKa = 7,5 100 C. Active secretion 50 + + + + + + + + + + + + + + 6 6,5 7 7,5 8 + + + % + + pKa = 6,5 + + 100 + Tubular transport system for - - + – Cations - Anions - - - - 50 - - - - - - - - % 6 6,5 7 7,5 8 - pH = 7,0 pH of urine 42 ‡ Drug Elimination Presystemic Elimination The morphological barriers of the body are illustrated on pp. 22–25. Depending on the physicochemical properties of drugs, intended targets on the surface or the inside of cells, or of bacterial organisms, may be reached to varying degrees or not at all.

Body weight may be broken down as illustrated in the pie-chart. Further subdivisions are shown in the panel opposite. The volume ratio of interstitial: intracellular water varies with age and body weight. On a percentage basis, interstitial fluid vol- Solid substances and structurally bound water 40% 20% 40% Intracellular water Extracellular water and erythrocytes ume is large in premature or normal neonates (up to 50% of body water), and smaller in the obese and the aged. The concentration (c) of a solution corresponds to the amount (D) of substance dissolved in a volume (V); thus, c = D/V.

However, this represents an apparent (notional) volume of distribution (Vapp), because an even distribution in the body is assumed in its calculation. Homogeneous distribution will not occur if drugs are bound to cell membranes (5) or to membranes of intracellular organelles (6) or are stored within organelles (7). In these cases, plasma concentration c becomes small and Vapp can exceed the actual size of the available fluid volume. Conversely, if a major fraction of drug molecules is bound to plasma proteins, c becomes large and the calculated value for Vapp may then be smaller than that attained biologically.

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