Predictive ADME

Absorption
Distribution Pharmacokinetic
Metabolism Bioavailability
Elimination

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Bioavailablity of Drugs (I)

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Bioavailability of Drugs (II)

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METABOLISME

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The barriers that a lipophilic drug has to
transverse along the intestinal absorption
process:
(1) dissolution/solubilization in the intestinal
milieu;
(2) limited absorption window;
(3) unstirred water layer;
(4) efflux pumps;
(5) intra-enterocyte metabolism; and
(6) first pass hepatic metabolism.

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Copyright © American Heart Association Page R L et al. Circulation 2005;111:230-239

Drug metabolism and countertransport by P-gp.

Drug metabolism and countertransport by P-gp. During absorption, drugs are metabolized by
intestinal cytochrome P450. P-gp assists by pumping drug back into intestinal lumen. Drugs that
evade intestinal metabolism enter portal blood and are subject to further biotransformation by
hepatic cytochrome P450. Most drugs undergo phase I metabolism in which metabolites may be
further conjugated or are directly eliminated by kidney. Small group of drugs may undergo phase8 II
metabolism with no prior biotransformation. Modified with permission from Reference 2.
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HIPERTENSI

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Renal artery stenosis (renovascular disease) Primary hyperaldosteronism

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ANTIHIPERTENSI

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ANTIHIPERTENSI – VASODILATOR

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ANTIHIPERTENSI – RENIN ANGIOTENSIN SISTEM (ACEI, ARB,

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ANTIHIPERTENSI – DIURETIK

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ANTIHIPERTENSI – DIURETIK

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PAIN

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Ulrich et al. Nature Reviews Cancer 6, 130–140 (February 2006) | doi:10.1038/nrc1801

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Ulrich et al. Nature Reviews Cancer 6, 130–140 (February 2006) | doi:10.1038/nrc1801

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Ulrich et al. Nature Reviews Cancer 6, 130–140 (February 2006) | doi:10.1038/nrc1801

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Possible intracellular sites at which insulin resistance develops

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Therapeutic targets of antidiabetic agents. Drug names in italic are those in development or
withdrawn from the market.

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