药物（代谢）动力学（PPT课件讲稿）pharmacokinetics

pharmacokinetics Department of pharmacology Yang Fang-ju(杨芳矩) 2010.3

pharmacokinetics Department of pharmacology Yang Fang-ju (杨芳矩) 2010.3

Section 1 drug process in the body o 1. classification of drug process in the body It includes absorption, distribution, metabolism. excretion o Metabolism and excretion are called elimination

Section 1 drug process in the body ⚫ 1. classification of drug process in the body ⚫ It includes absorption, distribution, metabolism, excretion. ⚫ Metabolism and excretion are called elimination

tissue. cells bind dissociation Blood plasma absorption Dissociated drug excretion B ound arug metabolite biotransformation Process of drugs in the body

Dissociated drug tissue, cells bind dissociation excretion Bound drug metabolite biotransformation Blood plasma absorption Process of drugs in the body

o 2. transportation of drugs across membranes o The absorption, distribution, biotransformation and excretion of a drug all involve its passage across cell membranes Transported model: ●(1) Passive diffusion o It transports along a concentration gradient ●※ It needs not metabolic energy ●※ it is usually determined by its pka, lipid- water partition coefficient, molecular weigh, and ph gradient in solution

⚫ 2. transportation of drugs across membranes ⚫ The absorption, distribution, biotransformation, and excretion of a drug all involve its passage across cell membranes. ⚫ Transported model: ⚫ ⑴Passive diffusion ⚫ It transports along a concentration gradient ⚫ ※ It needs not metabolic energy ⚫ ※ it is usually determined by its pKa, lipid￾water partition coefficient, molecular weigh, and pH gradient in solution

●① lipid soluble diffusion( simple diffusion) o The nonionized molecules are usually lipid soluble and can diffuse across the cell membrane 2 Filtration through pores o Hydrophilic lipid-insoluble substances can cross membranes through water-filled pores ●③ Passive facilitated diffusion o This flows the concentration gradient but dose not obey simple diffusion lows. It is believed to involve a carrier mechanism

⚫ ① lipid soluble diffusion (simple diffusion) ⚫ The nonionized molecules are usually lipid soluble and can diffuse across the cell membrane. ⚫ ② Filtration through pores ⚫ Hydrophilic lipid-insoluble substances can cross membranes through water-filled pores. ⚫ ③ Passive facilitated diffusion ⚫ This flows the concentration gradient but dose not obey simple diffusion lows. It is believed to involve a carrier mechanism

2) Active transport o This is a process in which a solute moves across membrane against an electrochemical gradient. Either against a concentration gradient or, if the solution is charged ●※ t transports against a concentration gradient ●※ t needs metabolic energy ●※| t inyo| ves carrier mechanisn,soit can become saturated ●※ t shows specificity for a particular type of chemical structure

⚫ (2) Active transport ⚫ This is a process in which a solute moves across membrane against an electrochemical gradient. Either against a concentration gradient or, if the solution is charged. ⚫ ※ It transports against a concentration gradient. ⚫ ※ It needs metabolic energy ⚫ ※ It involves carrier mechanism, so it can become saturated ⚫ ※ It shows specificity for a particular type of chemical structure

03. Ionicity influence lipid-soluble diffusion o the degree of dissociation of the drugs can express as Handerson-Hasselbalch equation:

⚫3. Ionicity influence lipid-soluble diffusion ⚫ the degree of dissociation of the drugs can express as Handerson-Hasselbalch equation:

weak acids weak bases HA-=H++A BH- H++B Ka=[H+IIa Ka=[H+[B-] IHA I LBHI IgKa=-1glHt]-Ig aj IgKa=-1gH]-1g B THA BHT pka-pH-Ig [A-1 pka=pH-1g IB IHA I I BH+ I That: pl H-pka=lga- pka -pH=lg[BH [HA I [B]

weak acids: weak bases: HA H+ + A- BH H+ + B Ka = [ H + ] [A- ] [ HA ] Ka = [ H +] [ B- ] ［BH］ -lgKa=-lg[H+ ]-lg [A- ] [HA] -lgKa=-lg[H+ ]-lg [B] [BH+ ] pka = pH - lg [ A - ] pka = pH - lg [ B ] [ HA ] [ BH+ ] That：pH - pka = lg [ A- ] pka - pH = lg [ BH ] [ HA ] [ B ]

10 PH -pka=[A-I 10 pka-pH=[HA] [HA I [B] When ph= pka when pH=pka THALAI [B=[BHI 10 PH -pka=[-] 10 pka-PH=L HA I [HA [B] When ph= pka when ph= pka [HA]=[A] B=BHI

10 pH -pka = [ A- ] 10 pka -pH = [ HA ] [ HA ] [ B ] When pH = pka, when pH = pka, [ HA ] = [ A ] [ B ] = [ BH ] 10 pH -pka = [ A- ] 10 pka -pH = [ HA ] [ HA ] [ B ] When pH = pka, when pH = pka, [ HA ] = [ A ] [ B ] = [ BH ]