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Effect of single‐walled carbon nanotubes on cytochrome P450 activity in human liver microsomes in vitro
Author(s) -
Asai Yuki,
Sakakibara Yukiko,
Inoue Rina,
Inoue Rikako,
Nadai Masayuki,
Katoh Miki
Publication year - 2018
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2133
Subject(s) - dextromethorphan , chemistry , chlorzoxazone , hydroxylation , microsome , econazole , phenacetin , cytochrome p450 , cyp3a4 , pharmacology , biochemistry , chromatography , in vitro , cyp2e1 , metabolism , enzyme , biology , ketoconazole , microbiology and biotechnology , antifungal
Single‐walled carbon nanotubes (SWCNTs) are made from a rolled single sheet of graphene with a diameter in the nanometer range. SWCNTs are potential carriers for drug delivery systems because antibodies or drugs can be loaded on their surface; however, their effect on the activities of cytochrome P450 (CYP) remains unclear. The aim of this study was to investigate the effect of two kinds of SWCNTs with different lengths (FH‐P‐ and SO‐SWCNTs) on human CYP activity. In addition, other nano‐sized carbon materials, such as carbon black, fullerene‐C 60 , and fullerene‐C 70 were also evaluated to compare their effects on CYP activities. Ten CYP substrates (phenacetin, coumarin, bupropion, paclitaxel, tolbutamide, S ‐mephenytoin, dextromethorphan, chlorzoxazone, midazolam, and testosterone) were used. Testosterone 6β‐hydroxylation and midazolam 1′‐hydroxylation, which are catalysed by both CYP3A4 and CYP3A5 in liver microsomes, were decreased by 25% and 45%, respectively, in the presence of 0.1 mg/ml SO‐SWCNT. Dextromethorphan O ‐demethylation, which is catalysed mainly by CYP2D6, was decreased by 40% in the presence of SO‐SWCNT. Other CYP activities, however, were not attenuated by SO‐SWCNT. FH‐P‐SWCNT, carbon black, fullerene‐C 60 , and fullerene‐C 70 at 0.1 mg/ml had no effect on CYP activities. The K i values for testosterone 6β‐hydroxylation, midazolam 1′‐hydroxylation, and dextromethorphan O ‐demethylation in liver microsomes were 136, 34, and 56 μg/ml, respectively. SO‐SWCNT was determined to be a competitive inhibitor of CYP3A4, CYP3A5, and CYP2D6. These results suggest that the effect of SO‐SWCNT differs among CYP isoforms, and that the inhibition potency depends on the physicochemical properties of the nanocarbons.