Pharmacokinetic drug interactions
Interactions changing the kinetics of drug can be clinically very relevant. Metabolic interactions occur the most and can cause prolonged presence of drugs in the body.
The four most important levels of interactions are listed below:
- The absorption of a drug can be reduced by another drug that binds or forms a complex before absorption.
E.g. tetracyclines and metal ions such as antacids, iron preparations, and calcium supplements.
- strong binding of a drug to plasma proteins can repress binding of other drugs by competitive displacement and thus increase their free plasma concentration.
E.g. digoxin and quinidine (kinedin): kinedin strongly binds plasma proteins and thus much more free digoxin is available.
- certain drugs can increase/decrease the activity of cP450 (CYP) enzymes and thus enhance/inhibit biotransformation of other drugs.
E.g. fluoxetine inhibits CYP2D6 metabolism of desipramine.
- drugs can actively or passively increase/decrease renal excretion of other drugs usually by competitive inhibition or change in urinary pH.
E.g. salicylates delay the excretion of penicillins and thus prolong their action.
See the website from the IUPUI for tables on CYP P450 interactions.
During what process would the concomitant use of lithium and furosemide likely interact?
Extra info: Lithium needs to be excreted through renal elimination. When given with furosemide (a diuretic), the lithium levels will increase due to the body’s attempt to conserve sodium and lithium ions.