Journal Journal of Pharmaceutical Sciences

[Title] Comparison of the Predictability of Human Hepatic Clearance for Organic Anion Transporting Polypeptide (OATP) Substrate Drugs Between Different In Vitro-In Vivo Extrapolation Approaches

[Authors] Saki Izumi, Yoshitane Nozaki, Takafumi Komori, Osamu Takenaka, Kazuya Maeda, Hiroyuki Kusuhara, and Yuichi Sugiyama

[Journal] Journal of Pharmaceutical Sciences

Supplementary Table 2

RB, fu,plasma, fu,blood, and clinical pharmacokinetic data of OATP substrate drugs

-, negligible; RB, blood-to-plasma drug concentration ratio; fu,plasma, drug unbound fraction in plasma; fu,blood, drug unbound fraction in blood; CLtot,plasma, plasma concentration-based total clearance; CLr,plasma, plasma concentration-based renal clearance; CLh,blood, blood concentration-based hepatic clearance; CLint,all,vivo, overall hepatic intrinsic clearance in vivo.

aRB and fu,plasma values are presented as mean ± SD of 9 (RB) or 6 (fu,plasma) healthy subjects.

bfu,blood values were calculated by dividing mean fu,plasma by mean RB.

cWhen body weight information was not given in the data source, 70 kg/man was used.

dCLh,blood = (CLtot,plasma – CLr,plasma)/RB. When CLh,blood can be calculated from multiple data sources, the mean value given in parenthesis was used for calculating CLint,all,vivo.

eCLint,all,vivo was calculated from the CLh,blood based on a dispersion model with a dispersion number of 0.17 and hepatic blood flow rate of 20.7 mL/min/kg.

fData from Caucasian.

gData from Chinese.

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