Factors influencing absorption 3.Effect of pH on drug absorption AWeakacid A drug passes through membranes more readily if it is uncharged. It is useful to consider three important body compartments: 50d compartment ·Plasma pH=7.4 B Weak base ·Stomach pH=2.0 Lipid Small intestine pH=8.0 Aspirin:absorption in the stomach Body Body Quinidine: absorption in the small compartment mpartment intestine 16
3. Effect of pH on drug absorption A drug passes through membranes more readily if it is uncharged. It is useful to consider three important body compartments: Factors influencing absorption 16 body compartments: • Plasma pH=7.4 • Stomach pH=2.0 • Small intestine pH=8.0 Aspirin: absorption in the stomach Quinidine: absorption in the small intestine
Factors influencing absorption 4.Blood flow to the absorption site Because blood flow to the intestine is much greater than the flow to the stomach,absorption from the intestine is favored over that from the stomach. 5.Contact time at the absorption surface If a drug moves through the Gl tract very quickly, as can happen with severe diarrhea,it is not well absorbed. 17
4. Blood flow to the absorption site Because blood flow to the intestine is much greater than the flow to the stomach, absorption from the intestine is favored over that from the stomach. Factors influencing absorption 17 intestine is favored over that from the stomach. 5. Contact time at the absorption surface If a drug moves through the GI tract very quickly, as can happen with severe diarrhea, it is not well absorbed
2.Drug Distribution Capillary Distribution is the delivery of drug from the systemic circulation to tissues. 18
2. Drug Distribution 18 Distribution is the delivery of drug from the systemic circulation to tissues
Factors influencing distribution Binding of drugs to plasma proteins Physiological barriers to drug distribution Blood flow Selective accumulation of drugs > 19
Binding of drugs to plasma proteins Physiological barriers to drug distribution Blood flow Factors influencing distribution 19 Selective accumulation of drugs
Factors influencing distribution 1.Binding of drugs to plasma proteins Drug molecule Plasma protein plasma protein binding rate [bound drug] bound X100% [bound drug][free drug] acidic drugs-albumin @basic drugs-lipoproteins or a1-acid glycoprotein (a1-AGP) 20
Factors influencing distribution 1. Binding of drugs to plasma proteins plasma protein binding rate Drug molecule Plasma protein 20 acidic drugs – albumin basic drugs – lipoproteins or α1-acid glycoprotein ( α1-AGP)