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静脉用上市溶液口服给药后依托泊苷的生物利用度:治疗和药物经济学视角

Bioavailability of etoposide after oral administration of the solution marketed for intravenous use: therapeutic and pharmacoeconomic perspectives.

作者信息

Aguilar Ponce J L, Flores-Picazo Y, Pérez-Urizar J, Castañeda-Hernández G, Zinser-Sierra J W, Dueñas-González A, Calderón-Flores E, Segura-Pacheco B A, de la Garza-Salazar J

机构信息

Instituto Nacional de Cancerología, México, D.F., Mexico.

出版信息

Arch Med Res. 1999 May-Jun;30(3):212-5. doi: 10.1016/s0188-0128(99)00014-7.

Abstract

BACKGROUND

Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES).

METHODS

Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. Plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and bioavailability parameters were calculated.

RESULTS

Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 +/- 0.30 micrograms/mL, AUC was 12.87 +/- 2.02 micrograms/mL and half-life was 6.72 +/- 0.97 h.

CONCLUSIONS

Considering that the pharmacokinetic aim is to maintain plasma concentrations between 0.5 and 1.0 microgram/mL for several hours while avoiding high concentrations, i.e., of 10 micrograms/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration.

摘要

背景

口服依托泊苷是静脉给药途径的合适替代方法;因此,已开发出商业胶囊。在这些胶囊在墨西哥上市之前,我们研究了静脉用依托泊苷溶液(IVES)口服后的药物生物利用度。

方法

8名成年癌症患者接受了50毫克口服依托泊苷剂量的IVES,在24小时内采集血样。通过高效液相色谱法测定血浆依托泊苷浓度,绘制血浆浓度-时间曲线,并计算生物利用度参数。

结果

口服IVES产生了足够的生物利用度曲线,因为Cmax为2.38±0.30微克/毫升,AUC为12.87±2.02微克/毫升,半衰期为6.72±0.97小时。

结论

考虑到药代动力学目标是在数小时内将血浆浓度维持在0.5至1.0微克/毫升之间,同时避免高浓度,即10微克/毫升或更高,口服50毫克依托泊苷作为IVES似乎是一种合适的给药选择。此外,就药物剂型和给药方式而言,口服IVES比静脉给药便宜得多。

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