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in vitro toxicology

Drug-drug interactions

Cyprotex is a specialist provider of ADME and PK services and provide a range of in vitro drug-drug interaction assays.

Drug Metabolism

The most common types of metabolic drug-drug interactions are the inhibition and induction of the drug metabolising enzymes. These interactions can cause increased or decreased drug exposures when two or more drugs are co-administered. For example, cytochrome P450 inhibition (CYP450) may increase the plasma levels of co-administered drugs leading to toxicity. Conversely, if a CYP450 enzyme is induced it may increase the metabolism of the co-administered compound; this can reduce plasma levels resulting in decreased efficacy or an increased formation of a toxic metabolite.

Cyprotex provide a range of services to investigate drug-drug interactions including cytochrome P450 inhibition, cytochrome P450 time dependent inhibition, cytochrome P450 induction (catalytic activity and/or mRNA assessment), PXR and AhR nuclear receptor activation and UGT inhibition as well as a range of other non-CYP mediated metabolism assays. Cyprotex also offer more detailed Ki service in order to determine the inhibitor affinity to the enzyme and indicate the type of inhibition observed. We can also offer a kinact/KI service to further characterize time dependent inhibition.

Investigating if any of the main CYP isoforms are involved in the in vitro metabolism of a drug is also important in determining if drug interactions may occur. Cyprotex provide a cytochrome P450 and UGT reaction phenotyping service as well as a non-CYP mediated reaction phenotyping service.

DDI Services

Drug Metabolism Services
cytochrome P450 and UGT reaction phenotyping
non-CYP mediated metabolism
cytochrome P450 induction
cytochrome P450 inhibition
cytochrome P450 Ki
PXR and AhR Nuclear Receptor Activation
time dependent inhibition (single point)
time dependent inhibition (IC50 shift)
time dependent inhibition (kinact/KI)
UGT inhibition
Drug Transporter Services
Caco-2 Permeability
MDCK-MDR1 permeability
P-gp Substrate Identification
BCRP Substrate Identification
Human SLC Transporter Substrate Identification (OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, OATP1A2, OATP2B1, OAT2, OAT4, OCTN2, PEPT1, PEPT2, NTCP)
Human MRP Transporter Substrate Identification
Preclinical Hepatic Oatp Uptake Transporter Substrate Identification (Rat Oatp1b2, Dog Oatp1b4 and Cynomolgus Monkey Oatp1b1)
P-gp inhibition
BCRP inhibition
Human SLC Transporter Inhibition (OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, OATP1A2, OATP2B1, OAT2, OAT4, OCTN2, PEPT1, PEPT2, NTCP)
BSEP and MRP Inhibition
Preclinical Hepatic Oatp Uptake Transporter Inhibition (Rat Oatp1b2, Dog Oatp1b4 and Cynomolgus Monkey Oatp1b1)
Other transporter assays available on request
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