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目的:评价贝沙罗汀在复发难治性皮肤T细胞淋巴瘤患者中的药物代谢动力学。方法:建立荧光液相色谱法,以乙腈、乙酸铵、乙酸等为流动相成分,在激发波长260 nm、发射波长430 nm的色谱条件下进行方法学考察及血药浓度测定。所得到的血药浓度以DAS 2.0药代动力学参数计算程序进行参数计算。皮肤T细胞淋巴瘤患者接受贝沙罗汀口服300 mg.m-2,qd,连用4周,进行单剂量和多剂量药代动力学分析。结果:建立的荧光液相色谱法在10～1 000 ng.mL-1之间线性关系良好(r=0.999 7),在空白血浆中20,100和800 ng.mL-1浓度的提取回收率分别为79.49%8,7.06%和78.56%。血药浓度测定结果显示,5例皮肤T-细胞淋巴瘤患者口服贝沙罗汀软胶囊300 mg.m-2,服药d 1和连续服药d 28的Cmax分别为366.31和652.44 ng.mL-1;Tmax分别为1.80和1.88 h;t1/2分别为2.56和3.18 h;AUC0～t分别为1 680.96和2 133.34ng.mL-1.h。结论:建立的荧光液相色谱法稳定,敏感性高。皮肤T-细胞淋巴瘤患者口服300 mg.m-2的贝沙罗汀软胶囊后吸收较快,连续服药d 28时峰浓度高于服药d 1时峰浓度近1倍,可见贝沙罗汀在受试者体内有一定的蓄积。
OBJECTIVE: To evaluate the pharmacokinetics of bexarotene in patients with relapsed and refractory cutaneous T-cell lymphoma. Methods: Fluorescence liquid chromatography (HPLC) was established. The mobile phase consisted of acetonitrile, ammonium acetate, acetic acid and so on. The methodological investigation and determination of plasma concentration were carried out under the conditions of excitation wavelength 260 nm and emission wavelength 430 nm. The resulting plasma concentration was calculated using the DAS 2.0 pharmacokinetic parameter calculation program. Patients with cutaneous T-cell lymphoma received bexarotene orally 300 mg.m-2 qd for 4 weeks for single-dose and multi-dose pharmacokinetic analysis. Results: The established fluorescence-based liquid chromatography showed a good linear relationship (r = 0.999 7) between 10-1 000 ng.mL-1 and the recoveries of 20, 100 and 800 ng.mL-1 in blank plasma were 79.49% 8,7.06% and 78.56%. The plasma concentrations of bexarotene capsules in 5 patients with cutaneous T-cell lymphoma were 300 mg.m-2, 366.31 and 652.44 ng · mL-1, respectively, for d 1 and continuous d 28 ; Tmax was 1.80 and 1.88 h respectively; t1 / 2 was 2.56 and 3.18 h, respectively; AUC0-t was 1 680.96 and 2 133.34 ng.mL-1.h respectively. Conclusion: The established fluorescence liquid chromatography is stable and sensitive. Skin T-cell lymphoma patients oral absorption of 300 mg.m-2 bexarotene soft capsules faster, continuous d 28 peak concentration was higher than the d 1 when the peak concentration of nearly 1-fold, bezaloderine There is some accumulation in the subject’s body.