Metabolism - Pharmacokinetics

Metabolism

·        Water soluble: excreted unchanged through the kidney

·        Lipid soluble: Can‟t be excreted by kidneys (reabsorbed straight away) so conjugated or metabolised ® water soluble ® excretion

·        Metabolism:

o   May result in activation of a pro-drug, active metabolites or inactive metabolites

o   Phase 1: oxidation, reduction, hydrolysis

o   Phase 2: conjugation, eg methylation, acetylation, glutamine, etc

o   Occurs in mainly in the liver, also in the lung, kidney, blood, small intestine, gut bacteria

·        1^st pass metabolism: high > 70%, e.g. lignocaine, GTN (no use taking them orally)

·        Examples of drug metabolic reactions:

·        Factors affecting metabolism: genetics, ethnicity, age, gender, pregnancy, liver disease, time of day, environment, diet, malnutrition, alcohol, other drugs