DDI & Polymorphism

Combined impact of drug-drug interaction and CYP polymorphism

Age of patient

Age >= 2 years

Age < 2 years ( months)

Age

months

Adult

substrate

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CYP metabolism is a minor pathway for the elimination of this drug. No relevant interaction with CYP inhibitors or inducers is expected.

Glucuronidation is a major pathway for the elimination of this drug. No relevant interaction with CYP inhibitors is expected. Some inducers (e.g. rifampicin) may lower its exposure.

substrate

Fraction metabolized by each CYP

Adults
Children

Warning!

Interactor

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interactor

Induction or Inhibition potency with respect to each CYP

Warning!

Genotypes

AUC ratios

Phenotype
Genotype

Show AUC ratios' interindividual distribution (5th to 95th percentiles)

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Definitions

AUC^XM*

AUC of the substrate given with an inhibitor or an inducer

AUC^XM* / AUC^XM

This ratio is useful for adapting the dose of the substrate in a patient in whom an optimal dose had been found but an interacting drug is added to the current treatment.

AUC^XM* / AUC^EM

This ratio is useful for adapting the initial dose of the substrate to be given to a patient whose genotype is known.

Limits and warnings

Phenotypes are defined with respect to FA (the Fraction of Activity of the CYP) as EM (Extensive Metabolizer,FA between 0.75 and 1.33); UM (Ultra Metabolizer, FA greater than 1.33); IM (Intermediate Metabolizer, FA between 0.25 and 0.75); PM (Poor Metabolizer, FA less than 0.25).
DDI predictions made on this page are NOT for patients with severe liver impairment.
Inhibition and inducing potencies depend on the dose of the inhibitor and the inducer respectively.
Induction takes several days to reach a steady-state, the AUC ratios are estimated at equilibrium, after repeated dosing of the inducer.
Some drugs have active metabolites (non exhaustive list: amitriptyline, diazepam, nebivolol, nelfinavir, propafenone, risperidone, tolterodine, tramadol). Here, the adjusted dose cannot be estimated with the usual formula, but on a case by case basis.
Some DDIs involve also protein binding displacement (phenytoin + valproate, warfarine S + bucolome). In this case, the reported AUC ratios are in fact the ratios of free AUCs.
DDI predictions on this page are only for drugs given PER OS.
DDI-PREDICTOR assumes that interactions are mediated only by CYPs. Other interactions, mediated e.g. by transporters (PgP, ...) are NOT taken into account.
DDI-PREDICTOR is NOT for interactions between more than two drugs.
DDI-PREDICTOR assumes linear kinetics, which is not true for e.g. perhexilline, phenytoin, voriconazole. In these cases, the calculated AUC ratios are approximate.
No genetic polymorphism is considered for cyp 3A4 and cyp 1A2.

Age of patient

Age

months

Adult

substrate

substrate

Interactor

interactor

Genotypes

AUC ratios

Definitions

AUCXM*

AUCXM* / AUCXM

AUCXM* / AUCEM

AUC^XM*

AUC^XM* / AUC^XM

AUC^XM* / AUC^EM