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Summary of Pharmacokinetics of Drug Interaction

Pharmacokinetic drug-drug interactions occur when a drug alters the disposition (absorption, distribution, elimination) of a coadministered agent.

Pharmacokinetic interactions may lead to the rise or the decrease of plasma drug concentrations. These modifications are variable in intensity but can cause contraindications of the association. The mechanisms of pharmacokinetic interactions involve drug metabolizing enzymes, drug transporters and orphan nuclear receptors that regulate at the transcriptional level the expression of enzymes and transporters.

The increase of drug plasma concentrations is mostly associated with the inhibition of enzymes and/or drug transport. The decrease of drug concentrations reflects the activation of orphan nuclear receptors by inducers that cause the rise of the expression of enzymes and drug transporters. Inhibition of drug metabolism or transport is kind of immediate (24-48h) while induction may be a slower process (7-10 days).

Complex situations is also observed with drugs that are both inducers and inhibitors (rifampin, ritonavir). they will cause the decrease and also the increase of the exposure of the combined agent betting on the duration of the association.