เภสัชจลนศาสตร ์ (Pharmacokinetics) และ …

1 (Pharmacokinetics) ( pharmacodynamics ).. (Drug-Body Interactions) .. ( pharmacodynamics ) (Pharmacokinetics).. 1. ( pharmacodynamics ) (Pharmacokinetics). 2. (absorption). 3. (distribution). 4. (metabolism). 5. (excretion). 1. ( pharmacodynamics ) (Pharmacokinetics). (Pharmacodymamics) . (what drug does to the body) .. (drug target) . (dose-response relationship). (Pharmacokinetics) . (what the body does to the drug) . 17 (absorption), (distribution), . (metabolism), (excretion) .. (onset) . (duration of action). 2. (Drug Absorption) (site of administration) plasma . (intravenous injection) . (Oral administration) .. - Gastrointestinal motility : .. - Splanchnic blood flow : .. - Particle size and formulation : Particle size . (dose) . particle size.

2 - Physicochemical factor : . Tetracycline .. (Sublingual administration) . rapid response gastric pH . metabolize systemic circulation portal circulation first pass metabolism Glyceryl trinitrate sublingual (Rectal Administration) .. 18 (Application to epithelial surfaces) . systemic circulation lipid solubility systemic circulation (transdermal patch) presystemic . first pass metabolism . (Inhalation) plasma concentration . systemic effect .. systemic side effect Bronchodilators ( ) . (aerosol). (Intravenous (IV) injection) . - . - systemic circulation . Bioavailability systemic circulation .. portal circulation . systemic circulation . systemic circulation . systemic circulation first pass metabolism presystemic metabolism bioavailability.

3 (Intravenous injection) systemic circulation Bioavailability . 1. (Drug Distribution). fluid compartment . physiological factors physicochemical properties .. , , , , , . 19 1. Permeability across barrier . capillary endothelial membrane . lipid insoluble . 2. Drug binding (free form) . ( bound form) . systemic circulation protein binding . 3. Fat : water partition lipid soluble drugs fat : water partition drug reservoir Thiopental . 3 stable reservoir . 2. (Drug Metabolism) Biotransformation . 2 . 1. Phase I reaction : oxidation, reduction, hydrolysis . reactive group chemically reactive toxicity . 2. Phase II reaction: conjugation substituent group . pharmacologically inactive lipid soluble .. Phase lipid solubility . Phase I Phase II reactions metabolism.

4 Metabolite .. 1. Enzyme Induction .. (metabolize) enzyme inducer . active substances . toxicity .. Enzyme inducer rifampin, ethanol, carbamazepine . enzyme inducer . 20 2. Enzyme Inhibition .. enzyme inhibitor enzyme inhibitor . cimetidine, ketoconazole, clarithromycin, grapefruit juice 3. Genetic polymorphisms .. 4. Disease . hepatitis, alcoholic liver disease, fatty liver disease, biliary cirrhosis .. 5. Age phase I reaction . conjugation (Phase II) . phase I phase II 2 .. 3. (Drug Excretion) .. polar compound high lipid solubility . lipid soluble polar compound . , , . gas vapor **. 21