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. 2020 Apr 24;11:505. doi: 10.3389/fphar.2020.00505

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Copyright © 2020 Yuan, Qiao, Yang, Yu, Sun, Qian, Zhang, Meng, Zhang and Wang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The impact of co-administration and the relationship of VRC drug concentration with ADRs. RVC, reversible visual changes; N/MA, nerval or mental abnormity; ALF, abnormal liver function; AA, abnormal audition; (A), the occurrence rate and frequency of all ADRs; (B), C_t (including C_max and C_min) in patients with and without (normal group) ADRs; (C), significant difference in patients unbound C_max with and without ADRs; the unbound C_max in patients without ADRs (792.8 ± 348.9 ng/ml, n=21) was significantly lower than those with nerval or mental abnormity (1187 ± 355 ng/ml, n=10, p=0.038), with reversible visual changes (1453 ± 693 ng/ml, n=13, p<0.01).; (D), The C_t in patient co-administration with CYP450 inhibitor esomeprazole (C_min=1355 ± 657 ng/ml, n=24; C_max=2354 ± 867 ng/ml, n=33) was significantly higher than those without CYP450 inhibitor (C_min=0.930 ± 0.581, n=318, p=0.018; C_max=1.657 ± 0.530, n=429, p<0.01); (E), significant difference of unbound C_max in plasma samples from patients co-administration with (1390 ± 541 ng/ml, n=28) or without high PPB medicine (971.1 ± 390.8 ng/ml, n=16, p=0.011).