Astemizole CYP3A4/5/7 substrate

Aprepitant can increase the levels of CYP3A4 substrates in the short-term, then reduce them within 2 weeks. Caution is advised. Note that the manufacturers of aprepitant specifically contraindicate its concurrent use with pimozide, terfenadine, astemizole or cisapride. 

CYP3A4 is involved in the metabolism of 80%-90% of all currently available drugs (Table 2). Its presence accounts for the majority of the cytochrome enzymes in the liver. It has attracted attention from both physicians and pharmaceutical companies, as there have been incidences of fatal drug interactions, which have resulted in the withdrawal of these drugs from the market (terfena-dine in 1997, astemizole in 1999, and cisapride in 2000). Combinations ofpotent CYP3A4 inhibitors and substrates can drive drug levels to the toxic range. The... 

Nefazodone is a weak inhibitor of CYP2D6 but a potent inhibitor of CYP3A4 and it increases plasma concentrations of drugs that are substrates of CYP3A4, such as alprazolam, astemizole, carbamazepine, ciclosporin, cisapride, terfenadine, and triazolam. 

Besides, the eompetitive substrates for CYP3A4 do not signifieantly give rise to drug-drug interaction, as could be seen with astemizole and terfenadine, by virtue of the fact that the parent molecule (loratadine) overwhelmingly lacks effect on rectifying channels located in the cardiac tissue. 

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