SLC superfamily的基因功能在許多內生性物質以及藥品的吸收、分佈、排除中佔有重要的角色，而OATPs則分類在其中的SLCO family。OATP1B1以及OATP1B3是兩個特異性表現在肝臟基底膜的成員，負責將受質由血液運送到肝細胞中。膽紅素以及pravastatin分別是OATP1B1內生性以及外生性的受質，過去的研究顯示男性與女性的膽紅素數值之間存在顯著差異，在臨床試驗中得到pravastatin的血中濃度曲線下面積具有顯著的性別差異，我們推測血液中膽紅素的差異影響OATP1B1的功能，造成pravastatin藥動參數的性別差異，觀察23位健康受試者在pravastatin給藥後的藥動參數後發現男性的pravastatin血中濃度曲線下面積的確較女性受試者低，但各項藥動參數卻不受血中膽紅素數值影響，暗示pravastatin的性別差異並非來自膽紅素的影響。進一步分析33位受檢者離體肝臟組織中OATPs以及其他轉錄因子的基因表現量以釐清pravastatin性別差異的原因，顯示男性OATP1B1蛋白質的肝臟表現量為女性的1.24倍(p=0.13)，此結果可以解釋男性受試者pravastatin的Cl/F為女性的1.5倍(p=0.13)。除了OATP1B1以外，許多基因的mRNA表現量也呈現性別差異，包括CYP3A4、CYP3A5、CAR、PXR、GR、LXR、HNF1α、HNF4α和STAT5b。分析基因間的相關性後發現HNF4α和STAT5b位居上游調控許多藥物排除基因的表現，並且可能是藥物排除基因如CYP3A4、OATP1B1產生性別差異的原因。

The OATPs are classified within the solute carrier family SLCO. OATP1B1 and OATP1B3 are considered to be two of liver specific sinusoidal membrane uptake transporters. Pravastatin and bilirubin are exogenous and endogenous OATP1B1 substrates respectively. When these two substrates exist in blood simultaneously, bilirubin may influence the normal function of OATP in pravastatin elimination. Consequently, OATP1B1-mediated clearance of dugs may attenuate. In the present study, we recruited 23 volunteers with the same OATP1B1 genotype and different serum bilirubin levels to see the effect of sex and serum bilirubin on pravastatin pharmacokinetics. In the result, serum bilirubin in normal range did not influence the pharmacokinetic parameter including AUC, Cmax, half life, Cl/F, k/F and Vd. On the other hand, we observed gender difference in Cl/F (M>F, 1.5x, p=0.13) suggesting that sex may affect the pharmacokinetics of pravastatin and possibly through the expression level of OATP1B1. We consequently collected 33 human liver samples to elucidate the gender difference in OATPs expression and the correlations between drug metabolism gene and other transcription factor. We found that OATP1B1 protein expression (M>F, 1.24x, p=0.13) which may be responsible for the difference in pravastatin pharmacokinetics. Using partial regression analysis, HNF4α and STAT5b were identified as the highest master regulator in the hierarchy of xenobiotic metabolism gene expression. In the conclusion, HNF4α and STAT5b may be responsible for the gender and inter-individual difference in xenobiotics metabolism.

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