藥物運輸器(drug transporters)對於藥品的吸收、分佈和排除扮演著重要的角色 ◦ 肝臟是排除和代謝藥品的主要器官之一 ◦ 在肝臟代謝藥品過程中，藥物代謝酵素與肝細胞膜上的運輸器是關鍵的影響因子 ◦ 肝細胞basolateral上的運輸器是藥品從血液中進入細胞內進行代謝的調控者◦ 有機陰離子運輸器 C (OATP-C) 主要表現在肝細胞的basolateral，它調控著許多內生性物質和藥品進入肝細胞進行代謝與排除 ◦ 另外，由於砷可以引起人類皮膚及血管病變並與多種癌症的形成具關連性;同時它也被使用於治療某些癌症 ◦ 但是它在人體內如何被運送，目前知道的並不多，探討它在人體內如何被運送是有其重要性 ◦ 因此，我們建立穩定表現OATP-C之細胞株並利用ICP-MS測量細胞內砷含量，同時也使用細胞毒性試驗來佐證在砷運輸過程中OATP-C是否扮演角色◦ 結果發現OATP-C可以增加細胞對arsenite和arsenate的uptake與細胞毒性；但是MMAV和DMAV則不受影響。Rifampin和taurocholic acid (OATP-C的受質)可以回復arsenite或arsenate在control和OATP-C cells間所產生之細胞毒性差異。因此由實驗結果發現OATP-C運送inorganic arsenic是GSH-dependent manner。
另一方面，近來有研究發現 OATP-C的基因多型性，會產生個體間對於藥物血中濃度和藥效之差異，也有文獻指出臨床上某些藥物交互作用的產生與運輸器有關◦ 因此我們分析在文獻上指出會影響藥物血中濃度之OATP-C SNPs在台灣族群之分布情形。我們利用AS-PCR和PCR-RFLP分析162位台灣人OATP-C之基因多型性，發現OATP-C*1a、OATP-C*1b、OATP-C*5和OATP-C*15的allele frequencies分別為22.2%、68.2%、0%和9.6%。並且以[3H]-estradiol-17b-D-glucuronide (E217bG)作為OATP-C的受質，利用競爭性抑制實驗探討臨床上常使用藥品中有那些藥品是OATP-C的受質，發現有五個藥品(ergoloid mesylates、ginkgo biloba、bromocriptine、ticlopidine 和clopidogrel)可以顯著抑制OATP-C運送[3H]-E217bG。接著以ticlopidine為研究標的，探討OATP-C基因多型性是否會影響其藥品動態學參數。由實驗得知OATP-C SNP (*1b)並不會影響ticlopidine血中濃度。同時另一方面也分析臨床上併用ticlopidine與ergoloid mesylates或ginkgo biloba時，是否會產生交互作用。結果發現ergoloid mesylates會分別減少ticlopidine 30%AUC與29%Cmax；但ginkgo biloba不會。
另外我們也發現bromocriptine可以顯著抑制OATP-C運送[3H]-E217bG。經由進一步實驗發現bromocriptine和erythromycin抑制OATP-C運輸[3H]-E217bG之IC50分別為0.12 uM和9.20 uM，並且erythromycin可以抑制OATP-C運送bromocriptine。因此文獻上指出erythromycin可以增加bromocriptine之bioavailability，其機制可能是經由抑制OATP-C運送bromocriptine進入肝臟代謝。由以上實驗可以得知OATP-C的確是一個重要的運輸器，其功能與基因多型對藥物的影響，仍須更進一步研究。

Drug transporters express in various tissues, such as the intestine, brain, liver, and kidney. Transporters play key roles in the absorption, distribution and elimination of drugs. The organic anion transporting polypeptide C (OATP-C) expresses on the basolateral membrane of hepatocytes and has broad substrate specificity. Transporting of arsenic by OATP-C is studied. We measured the uptake of arsenic in control and OATP-C transfected cells by ICP-MS, and we compared the relative cytotoxicity of arsenite, arsenate, MMAV, and DMAV by MTT assay. Transfection of OATP-C increased uptake and cytotoxicity of arsenate and arsenite, but not those of MMAV or DMAV. Rifampin and taurocholic acid (substrates of OATP-C) reversed the increased toxicity of arsenate and arsenite in OATP-C–transfected cells. The results suggest that OATP-C can transport inorganic arsenic in a GSH-dependent manner.
Genetic polymorphism of OATP-C transporter also plays an important role in pharmacokinetics and pharmacological effects of drugs. The genetic polymorphisms of OATP-C in the Taiwanese population were analyzed. The allele frequencies of OATP-C*1a, OATP-C*1b, OATP-C*5, and OATP-C*15 were 22.2%, 68.2%, 0%, and 9.6%, respectively, in 162 Taiwanese subjects.
Substrate inhibition of OATP-C was also studied by using tritium-labeled estradiol-17b-D-glucuronide (E217bG). Five (ergoloid mesylates, ginkgo biloba, bromocriptine, ticlopidine and clopidogrel) neurological drugs significantly inhibited the OATP-C-mediated uptake of E217bG. We also investigated the pharmacogenetic effects of OATP-C*1a and *1b haplotypes on the pharmacokinetics of ticlopidine in healthy subjects. The data indicated that, in comparison with the wild-type (OATP-C*1a/*1a) genotype, OATP-C variant (*1b/*1b) was not significantly different in the pharmacokinetics of ticlopidine. We also investigated whether clinically significant interactions occur between ticlopidine and ginkgo biloba or ergoloid mesylates in humans. Coadministration of ergoloid mesylates decreased the area under plasma concentration curve (AUC0-12) of ticlopidine by 30% and the peak plasma drug concentration (Cmax) by 29%. Ginkgo biloba did not significantly change any of ticlopidine’s pharmacokinetic parameters.
We also found that bromocriptine significantly inhibited the OATP-C-mediated uptake of E217bG. Both bromocriptine (IC50 0.12 uM) and erythromycin (IC50 9.20 uM) significantly inhibited the OATP-C-mediated uptake of [3H]-E217bG, and erythromycin inhibited the uptake of bromocriptine by OATP-C. The results suggest the literature data of increased bromocriptine bioavailability by erythromycin is by inhibiting the OATP-C-mediated uptake of bromocriptine in the liver.

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