Pharmacokinetics Asst Prof Dr Inam S. Arif

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Presentation transcript:

Pharmacokinetics Asst Prof Dr Inam S. Arif Pharm.dr.isamalhaj@uomustansiriyah.edu.iq isamalhaj@yahoo.com

Absorption of Drugs (mechanisms & factors controlling) The transfer of D from site of administration to bloodstream via several mechanisms Rate & Efficiency Mechanisms of absorption of drugs from GIT Passive diffusion Facilitated diffusion Active transport Endocytosis & exocytosis

Mechanisms of absorption of drugs from GIT

Factors Influencing Absorption 1- Effect of pH Effective conc. of the permeability form Ionization constant (pKa)

The effect of pH on drug ionisation. Acidic conditions (low pH, high H+ concentrations) push the equilibrium of acidic drugs towards their un ionised (protonated) form, and basic drugs towards their ionised form. Basic conditions (high pH) have the opposite effect.

Partitioning of acidic and basic drugs across a pH gradient Partitioning of acidic and basic drugs across a pH gradient. Only the un ionised forms (DH and D) are able to diffuse across the membrane. In urine (pH 6), the un ionised acidic drug (DH) can be readily reabsorbed into the plasma, where its ionised form (D−) becomes concentrated, while the ionised basic drug (D+) is trapped within the urine. Alkalinising the urine would reduce reabsorption of the acid drug and enhance that of the basic drug.

Factors Influencing Absorption (cont.) 2- Blood flow 3- Surface area 4- Contact time (diarrhea, parasympathetic, sympathetic, anticholinergic) 5- Expression of P-glycoprotein (expression, resistance)

Expression of P-glycoprotein Multidrug transmembrane transporter ptn Expression Function Multidrug resistance

Bioavailability The fraction of the administered drug that reaches the systemic circulation

Factors Influencing Bioavailability: 1st-pass effect Solubility of D Chemical instability Nature of D formulation Bioequivalence Therapeutic equivalence

Drug Distribution The process by which a drug reversibly leaves the blood stream and enters interstitium (ECF) and tissues capillary permeability, T vol., pl ptns binding, & relative lipophilicity Blood Flow (CO & local BF) Capillary permeability (capillary structure, chemical nature)e.g. levodopa Binding to pl ptns & tissues (acrolein metabolite of cyclophosphamide) lipophilicity

Liver and Brain Capillaries

Volume of Distribution Apparent volume of distribution: the fluid volume required to contain the entire drug in the body at the same concentration measured in the plasma Plasma compartment ECF Total body water

The Main Body Fluid Compartments

Volume of Distribution (cont.) Apparent volume of distribution (Vd) Determination of volume of distribution Plasma half life (t1/2) Effect of Vd on t1/2

Plasma Drug Concentration after Single Injection