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他汀类药物在前列腺组织中的浓度具有亚型和剂量依赖性。

Statin Concentration in Prostatic Tissue is Subtype- and Dose-dependent.

作者信息

Chavarriaga Julian, Penn Linda Z, Khurram Najia, Lajkosz Katherine, Longo Joseph, Chen Eric, Fleshner Neil, van der Kwast Theodorus, Hamilton Robert J

机构信息

Division of Urology, Department of Surgical Oncology, University Health Network & University of Toronto, Toronto, ON, Canada; Cancer Treatment and Research Centre (CTIC) Luis Carlos Sarmiento Angulo Foundation, Bogota, Colombia.

Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

出版信息

Urology. 2024 Dec;194:172-179. doi: 10.1016/j.urology.2024.08.059. Epub 2024 Aug 31.

Abstract

OBJECTIVE

To evaluate for the first time, comparative serum and prostate tissue concentrations of lipophilic and hydrophilic statins.

METHODS

After reviewing all patients who underwent radical prostatectomy between 1993 and 2019, we selected 80 patients taking atorvastatin (lipophilic) or rosuvastatin (hydrophilic) for cholesterol control and with available banked fresh-frozen tissue from the prostatectomy. Primary endpoint was serum and prostate statin concentration measured by HPLC-mass spectrometry analysis. Serum/prostate statin concentrations were compared between patients on atorvastatin and rosuvastatin, and patients receiving high- and low-dose statin, using the Mann-Whitney U test.

RESULTS

In total, 39 patients were taking atorvastatin and 41 were taking rosuvastatin. Thirty-eight and 42 were taking high- and low-dose statin, respectively. Statin concentration was measurable in the prostatic tissue of 15 patients (38.4%) taking atorvastatin (33.3% high-dose vs 42.8% low-dose) compared to 22 (53.6%) taking rosuvastatin (55% high-dose vs 52.3% low-dose). Median tissue concentration of rosuvastatin was greater than atorvastatin (3.98 ng/g vs 0.96 ng/g, P <.001). Dose-dependency was observed: median prostate concentration was higher in those taking high-dose versus low-dose statin for both atorvastatin (1.22 ng/g vs 0.79 ng/g, P = .69) and rosuvastatin (5.21 ng/g vs 1.99 ng/g, P <.001).

CONCLUSION

We have shown, for the first time, that lipophilic and hydrophilic statins can be measured in the prostate of patients with prostate cancer and that the concentrations are dependent on dose. Moreover, rosuvastatin, a hydrophilic statin, achieves a 4-fold higher concentration in the prostate.

摘要

目的

首次评估亲脂性和亲水性他汀类药物在血清和前列腺组织中的浓度差异。

方法

回顾1993年至2019年间接受根治性前列腺切除术的所有患者,我们选择了80名服用阿托伐他汀(亲脂性)或瑞舒伐他汀(亲水性)以控制胆固醇且有前列腺切除术中留存的新鲜冷冻组织的患者。主要终点是通过高效液相色谱-质谱分析测量的血清和前列腺他汀类药物浓度。使用曼-惠特尼U检验比较服用阿托伐他汀和瑞舒伐他汀的患者之间以及接受高剂量和低剂量他汀类药物的患者之间的血清/前列腺他汀类药物浓度。

结果

总共39名患者服用阿托伐他汀,41名患者服用瑞舒伐他汀。分别有38名和42名患者服用高剂量和低剂量他汀类药物。在服用阿托伐他汀的15名患者(38.4%)的前列腺组织中可检测到他汀类药物浓度(高剂量组为33.3%,低剂量组为42.8%),而服用瑞舒伐他汀的22名患者(53.6%)中可检测到(高剂量组为55%,低剂量组为52.3%)。瑞舒伐他汀的中位组织浓度高于阿托伐他汀(3.98 ng/g对0.96 ng/g,P <.001)。观察到剂量依赖性:阿托伐他汀(1.22 ng/g对0.79 ng/g,P =.69)和瑞舒伐他汀(5.21 ng/g对1.99 ng/g,P <.001)服用高剂量他汀类药物的患者前列腺中位浓度均高于服用低剂量的患者。

结论

我们首次表明,亲脂性和亲水性他汀类药物可在前列腺癌患者的前列腺中检测到,且浓度取决于剂量。此外,亲水性他汀类药物瑞舒伐他汀在前列腺中的浓度高出4倍。

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