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首页> 美国卫生研究院文献>British Journal of Cancer >Randomized comparison of etoposide pharmacokinetics after oral etoposide phosphate and oral etoposide.
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Randomized comparison of etoposide pharmacokinetics after oral etoposide phosphate and oral etoposide.

机译：口服依托泊苷磷酸盐和口服依托泊苷后的依托泊苷药代动力学的随机比较。

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摘要

Etoposide phosphate is a water-soluble prodrug of etoposide. The plasma pharmacokinetics of etoposide following oral administration of etoposide phosphate or oral etoposide were compared. Seventeen patients with solid tumours were enrolled to receive oral etoposide phosphate 125 mg m(-2) on days 1-5 every 3 weeks, with escalation to 175 mg m(-2) from course 3 when possible. Patients were randomized to receive oral etoposide phosphate or oral etoposide on day 1 of course 1 and the alternative compound on day 1 of course 2. Fifteen patients received two or more courses and were evaluable for pharmacokinetic comparisons. The median AUC(inf) (area under the concentration vs time curve from zero to infinity) of etoposide was 77.7 mg l(-1) h after etoposide phosphate (95% CI 61.3-100.5) and 62.0 mg l(-1) h after oral etoposide (95% CI 52.2-76.9). The difference in favour of etoposide phosphate was borderline significant: median 9.9 mg l(-1) h (95% CI 0.1-32.8 mg l(-1) h; P = 0.05). However, the inter-patient variability of etoposide AUC(inf) was not improved (coefficients of variation 42.3% and 48.4%). Etoposide phosphate was undetectable in plasma after oral administration. Toxicities of oral etoposide phosphate were not different from those known for etoposide. In conclusion, oral etoposide phosphate does not offer a clinically relevant benefit over oral etoposide.
机译：依托泊苷磷酸酯是依托泊苷的水溶性前药。比较口服口服依托泊苷磷酸盐或口服依托泊苷后依托泊苷的血浆药代动力学。每3周1-5天招募17例实体瘤患者接受口服依托泊苷磷酸盐125 mg m（-2），并在可能的情况下从第3疗程升级至175 mg m（-2）。患者在第1疗程的第1天随机接受口服依托泊苷磷酸盐或口服依托泊苷，在第2疗程的第1天接受替代化合物。15例患者接受了2疗程或更多疗程，可以进行药代动力学比较。依托泊苷磷酸酯（95％CI 61.3-100.5）和62.0 mg l（-1）h后，依托泊苷的AUC（inf）中位数（浓度与时间曲线从零到无穷大下的面积）为77.7 mg l（-1）h口服依托泊苷后（95％CI 52.2-76.9）。依托泊苷磷酸酯的支持率差异显着：中位数为9.9 mg l（-1）h（95％CI 0.1-32.8 mg l（-1）h； P = 0.05）。但是，依托泊苷AUC（inf）的患者间变异性并未得到改善（变异系数分别为42.3％和48.4％）。口服后血浆中未检出依托泊苷磷酸盐。口服依托泊苷磷酸盐的毒性与依托泊苷已知的毒性相同。总之，口服依托泊苷磷酸酯没有提供比口服依托泊苷临床相关的益处。

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