Impact of Intestinal CYP2C19 Genotypes on the Interaction between Tacrolimus and Omeprazole, but Not Lansoprazole, in Adult Living-Donor Liver Transplant Patients

• DOI: 10.1124/dmd.108.025833
• Publication Date: 2009-01-13T01:55:01Z
• Authors: Keiko Hosohata; Satohiro Masuda; Toshiya Katsura; Yasutsugu Takada; Toshimi Kaido; Yasuhiro Ogura; Fumitaka Oike; Hiroto Egawa; Shinji Uemoto; Ken-ichi Inui
• Keywords: Lansoprazole

To assess the effects of intestinal cytochrome P450 2C19 on interaction between tacrolimus and proton pump inhibitors, we examined concentration/dose ratio [(ng/ml)/(mg/day)] coadministered with omeprazole (20 mg) or lansoprazole (30 to 89 adult living-donor liver transplant patients postoperative days 22 28, considering <i>CYP2C19</i> genotypes native intestine graft liver, separately. The was significantly higher in two variants (<i>*2</i> <i>*3</i>) for CYP2C19 (median, 6.38; range, 1.55–22.9) than wild-type homozygotes 2.11; 1.04–2.54) heterozygotes 0.52–4.33) (<i>P</i> = 0.010), but extent increase attenuated by carrying allele even when were <i>CYP3A5*1</i> noncarriers. Conversely, polymorphisms both little influenced lansoprazole, noncarriers showed carriers. Furthermore, our experiments vitro revealed that had a stronger inhibitory effect CYP3A5-mediated metabolism omeprazole, although not (IC₅₀ 19.9 ± 13.8 μM 53.7 6.1 omeprazole). Our findings suggest plays relatively greater role it does so CYP3A5 might be masked associated genotype.