浙江大学医学院：《药理学 Pharmacology》课程教学资源（PPT讲稿）药物代谢动力学 Pharmacokinetics、影响药物作用的因素 Factors Influencing Drug Effects

Part 2 Pharmacokinetics 药物代谢动力学

Part 2 Pharmacokinetics 药物代谢动力学

Dose of drug administered sorption Drug concentration Distribution Drug in tissues in systemic circulation of distribution Elimination Kinetics Drug metabolized or excreted Models Drug concentration at site of action Parameters

Kinetics Models Parameters

0 2. Transport of Drug in the body A aqueous B lipid cell Ccarriers D endocytosis channels in the membranes (transporters exocytosis intercellular (into or out of junctions cells) Lumen Interstitium ●。 Mechanisms of drug permeation across cell membrane

2. Transport of Drug in the Body Mechanisms of drug permeation across cell membrane A. aqueous channels in the intercellular junctions B. lipid cell membranes C. carriers (transporters) (into or out of cells) D. endocytosis exocytosis

u 2.1 Transmembrane Transport of Drugs u(1) Non-carrier Transport Simple diffusion(简单扩散/单纯扩散) Filtration(滤过) A, aqueous B. lipid cell channels in the membranes tercellular unctions Ju Lumen

2.1 Transmembrane Transport of Drugs (1) Non-carrier Transport Simple diffusion（简单扩散/单纯扩散） Filtration（滤过）

d(2) Carrier-mediated Transport 口a. Active transport o Characteristics of active transport Involving specific carrier(transporter) o Energy-dependent o Saturability o Competition at same carrier Moving against concentration gradient (up-hill

(2) Carrier-mediated Transport a. Active transport Characteristics of active transport Involving specific carrier (transporter) Energy-dependent Saturability Competition at same carrier Moving against concentration gradient (up-hill)

目b. Facilitated diffusion(易化扩散) o(transporter-mediated diffusion) ccarriers D. endocytosis transporters) exocytosis into or out of o Involving specific carriers(transporter) cells o Energy-independent o Saturability o Competition with other drugs o Concentration gradient(down-hill) 口(3) Endocytosis/ exocytosis(入胞/出胞)

b. Facilitated diffusion（易化扩散） (transporter-mediated diffusion) Involving specific carriers (transporter) Energy-independent Saturability Competition with other drugs Concentration gradient(down-hill) (3) Endocytosis/exocytosis（入胞/出胞）

口 Another classification u Passive transport Simple diffusion(简单扩散/单纯扩散 口 Filtration(滤过) 口 Facilitated diffusion(易化扩散) 口 Active transport 口 Active transport(主动转运) Pinocytosis/exocytosis(入胞/出胞)

Another classification Passive transport Simple diffusion（简单扩散/单纯扩散） Filtration（滤过） Facilitated diffusion（易化扩散） Active transport Active transport (主动转运) Pinocytosis/exocytosis（入胞/出胞）

口A. Simple diffusion Most drugs are weak acids or bases Weak acid Their diffusion Weak base passing through cell Lipid membrane depen ds Lipid membrane membrane the lipid-soluble state BH (un-ionized form) HA B A HA Body Bod Body Bod compartment compartmen compartment compartment

A . Simple diffusion Most drugs are weak acids or bases. Their diffusion passing through cell membrane depends the lipid -soluble state (un -ionized form)

u Determinants of simple diffusion For most drugs of small molecules(usually are weak acids or weak bases ) o Lipid-soluble or un-ionized forms o pKa of the drug and pH of the body fluid u The pKa is the ph at which the concentrations of the ionized and un-ionized forms are equal

Determinants of simple diffusion For most drugs of small molecules (usually are weak acids or weak bases): Lipid-soluble or un-ionized forms pKa of the drug and pH of the body fluid The pKa is the pH at which the concentrations of the ionized and un-ionized forms are equal

o Henderson-Hasselbalch equation Weak acid drugs: PH-pKa=log(a/Had pKa-pH=log(田HA/[A1) Weak base drugs pKa-PH=log( bh|/BD) PH-pKa= log(b/BiD)

Henderson-Hasselbalch equation Weak acid drugs: pH - pKa = log ( [A- ] / [HA] ) pKa - pH = log ( [HA] / [A- ] ) Weak base drugs: pKa - pH = log ( [BH+ ] / [B] ) pH - pKa = log ( [B] / [BH+ ] )