Smith D B, Margison J M, Lucas S B, Wilkinson P M, Howell A
Cancer Chemother Pharmacol. 1987;19(2):138-42. doi: 10.1007/BF00254566.
The clinical pharmacology of 4-demethoxydaunorubicin (4-DMDNR) was studied in 28 patients with advanced breast cancer, using a sensitive reverse-phase HPLC technique. All patients had normal renal and hepatic function. The serum levels of 4-DMDNR after a single i.v. bolus injection followed a triple exponential decay curve (T 1/2 alpha = 9.6 min, T 1/2 beta = 3.2 h and T 1/2 gamma = 34.7 h) and conformed to a three-compartment model. Comparison of the area under the curve (AUC) and urinary excretion for the oral and i.v. routes suggests an oral bioavailability of approximately 24%. In patients treated with a schedule of weekly oral administration for periods of up to 12 months there was no significant alteration in either AUC or elimination half-life for the parent drug or its principal metabolite 13-OH4DMDNR. Moreover, there was no evidence of accumulation of the metabolite although measurable amounts were present 7 days after administration of 4-DMDNR.
采用灵敏的反相高效液相色谱技术，对28例晚期乳腺癌患者进行了4-去甲氧基柔红霉素（4-DMDNR）的临床药理学研究。所有患者的肾功能和肝功能均正常。单次静脉推注后4-DMDNR的血清浓度呈三指数衰减曲线（T 1/2α = 9.6分钟，T 1/2β = 3.2小时，T 1/2γ = 34.7小时），符合三室模型。口服和静脉给药途径的曲线下面积（AUC）和尿排泄比较表明，口服生物利用度约为24%。在接受长达12个月每周口服给药方案治疗的患者中，母体药物或其主要代谢物13-OH4DMDNR的AUC或消除半衰期均无显著变化。此外，尽管在给予4-DMDNR 7天后可检测到代谢物，但没有证据表明代谢物会蓄积。
