In part, the effects are due to a down-regulation of ABC-transporter proteins (P-gp, MRP1, and BCRP), metabolic genes (GST, CYP3A4
, and PXR) and an up-regulation of caspase family genes.
We therefore set out to assess the relative contributions of CYP3A5 and CYP3A4
to the formation of the main tacrolimus metabolite (13-O-demethyltacrolimus), using cDNA-expressed enzymes and a bank of human liver microsomes derived from low and high CYP3A5 expressers.
This substance inhibits CYP3A4
and CYP1A2, and--if it is taken concurrently with clozapine or olanzapine--the drug's side effects may appear at a lower dosage.
The inhibitory effects of miltirone on the activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4
were investigated with individual probe substrates in pooled HLMs via four reactions including phenacetin 0-deethylation, tolbutamide hydroxylation, dextromethorphan 0-demethylation and testosterone 6[beta]-hydroxylation, respectively.
In particular, the NNRTIs metabolised by CYP3A4
have shown to interact with PIs, which are inhibitors of CYP3A4
, especially ritonavir, a potent inhibitor.
It is reported that xanthone derivatives from mangosteen extract inhibited the metabolism of CYP2C9 and CYP3A4
substrates in both competitive and linear-mixed inhibition manners, while the inhibition mode of CYP1A2 was linear-mixed (Foti et al.
We investigated CYP3A4
mRNA expression in 31 human blood samples from healthy volunteers (20 males and 11 females; mean age, 29 years; range, 20-64 years) and in three human liver samples obtained from the International Institute for the Advancement of Medicine (Exton, PA).
Coadministration of strong CYP3A4
inducers, such as rifampin, carbamazepine, St.
Consider the potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4
(alprazolam, triazolam) when administering with AKYNZEO.
Assurance that prescribers would be fully apprised of the serious risks of hypotension and syncope associated with the drug, exacerbation of those side effects when combined with alcohol or a CYP3A4
inhibitor--and the modest effects over placebo --was cited by several of the panelists who voted in favor of approval.
Oral contraceptives, weak CYP3A4
inhibitors, were allowed in the three studies, but other CYP3A4
inhibitors, including fluticasone and grapefruit, were among the exclusion criteria.
In humans, MA only weakly inhibited CYP3A4
activity in human liver microsomes and specific CYP3A4
isoform with [IC.