近日，芝加哥醫(yī)學大學科學家發(fā)現(xiàn)一天八盎司葡萄柚汁可以減緩身體對西羅莫司的代謝,。在8月Clinical Cancer Research雜志上刊登的一項臨床試驗研究數(shù)據(jù)顯示,，癌癥患者每天喝一杯柚子汁能達到服用抗癌藥物類似的好處,。柚子汁也可以幫助患者避免因服用高劑量的藥物所帶來的副作用，同時也可減少用藥成本,。
他們觀察到,，喝八盎司柚子汁的患者西羅莫司代謝水平提高了350％，而每天服用減慢新陳代謝的一種藥物酮康唑的患者,，西羅莫司代謝水平提高了500％,。
葡萄柚汁可以抑制腸道中的酶，這打破西羅莫司和其他一些藥物的吸收,。這一效果僅僅在使用葡萄柚汁開始的幾個小時內(nèi),，研究人員指出葡萄柚汁的功效會逐天慢慢消失。葡萄柚汁以及具有類似機制的藥物可顯著增加許多藥物的血藥濃度,，但長期以來一直被認為過量是危害的,，相反，這項最新研究發(fā)現(xiàn)葡萄柚汁可以通過某種途徑增加西羅莫司的可用性和有效性,。（生物谷：Bioon.com)
編譯自：Grapefruit Juice Helps Anti-Cancer Drug Work Better
doi:10.1158/1078-0432.CCR-12-0110
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Phase I Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients
Ezra E.W. Cohen1,5, Kehua Wu1, Christine Hartford2, Masha Kocherginsky3, et al.
Purpose: Sirolimus is the eponymous inhibitor of the mTOR; however, only its analogs have been approved as cancer therapies. Nevertheless, sirolimus is readily available, has been well studied in organ transplant patients, and shows efficacy in several preclinical cancer models.
Experimental Design: Three simultaneously conducted phase I studies in advanced cancer patients used an adaptive escalation design to find the dose of oral, weekly sirolimus alone or in combination with either ketoconazole or grapefruit juice that achieves similar blood concentrations as its intravenously administered and approved prodrug, temsirolimus. In addition, the effect of sirolimus on inhibition of p70S6 kinase phosphorylation in peripheral T cells was determined.
Results: Collectively, the three studies enrolled 138 subjects. The most commonly observed toxicities were hyperglycemia, hyperlipidemia, and lymphopenia in 52%, 43%, and 41% of subjects, respectively. The target sirolimus area under the concentration curve (AUC) of 3,810 ng-h/mL was achieved at sirolimus doses of 90, 16, and 25 mg in the sirolimus alone, sirolimus plus ketoconazole, and sirolimus plus grapefruit juice studies, respectively. Ketoconazole and grapefruit juice increased sirolimus AUC approximately 500% and 350%, respectively. Inhibition of p70 S6 kinase phosphorylation was observed at all doses of sirolimus and correlated with blood concentrations. One partial response was observed in a patient with epithelioid hemangioendothelioma.
Conclusion: Sirolimus can be feasibly administered orally, once weekly with a similar toxicity and pharmacokinetic profile compared with other mTOR inhibitors and warrants further evaluation in studies of its comparative effectiveness relative to recently approved sirolimus analogs.
