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Absorption, distribution, metabolism and excretion:吸收,分布,代谢和排泄.ppt
Absorption, distribution, metabolism and excretion relevant to ALL drugs large research/development area frequent cause of failure of treatment failure of compliance failure to achieve effective level produce toxic effects can enhance patient satisfaction with treatment Learning objectives Know the processes involved in ADME of drugs Know how these processes may affect the action of xenobiotics Appreciate how these processes can affect the outcome of the treatment of patients with drugs Appreciate how differences in these processes between patients can affect therapy Know how these processes have been exploited to improve therapy Be able to exemplify the above Passage through lipid membranes diffusion through gaps between cells (glomerulus = 68K; capillary 30K) passage through the cell membrane diffuse through pore (very small; use dependent) carrier mediated transport (specific, saturable; Fe in gut; L-DOPA at blood-brain barrier; anion/cation transport in kidney) pinocytosis (insulin in CNS; botulinum toxin in gut) diffusion through lipid of cell membrane (depends on AREA, DIFFUSION GRADIENT, DIFFUSION COEFFICIENT, LIPID SOLUBILITY) Weak acids and weak bases Routes of administration Enteral; oral, sub-lingual (buccal), rectal Parenteral; iv, im, sc, id, it, etc. Surface; of skin, of lungs? for local or systemic effect? Inhalation; local or systemic effect? Vaginal; (usually local) Eye; (usually local) Factors affecting oral absorption Disintegration of dosage form Dissolution of particles Chemical stability of drug Stability of drug to enzymes Motility and mixing in GI tract Presence and type of food Passage across GI tract wall Blood flow to GI tract Gastric emptying time Bioavailability the proportion of the drug in a dosage form available to the body i.v injection gives 100% bioavailability. Calculated from comparison of the area under the curve (AUC) relating plasma concentration to time for iv dosage compared with other route. Says nothing about e
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