PHARMACOKINETICS OF INTRAVESICAL DOXORUBICIN IN SUPERFICIAL BLADDER-CANCER PATIENTS
PHARMACOKINETICS OF INTRAVESICAL DOXORUBICIN IN SUPERFICIAL BLADDER-CANCER PATIENTS
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DOI：
10.1016/s0022-5347(17)32742-8
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发表时间：
1994-08-01
影响因子：
6.6
通讯作者：
AU, JLS
中科院分区：
文献类型：
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作者：
CHAI, M;WIENTJES, MG;AU, JLS
对8例有浅表性膀胱癌病史的膀胱灌注阿霉素的尿液和血浆药代动力学进行了研究。患者每周接受6次40 mg治疗。阿霉素20 ml。生理盐水可检测到阿霉素（0.2 ng/ml）。ml.或更多）。最大浓度范围为0.5至4.5纳克/升。ml. (mean 1.4）。在治疗2期间，在8名患者中的7名患者的血浆中未检测到阿霉素，并且在治疗4期间，在任何患者中均未检测到阿霉素。由于导管插入术后残余尿稀释，给药后5分钟时尿液中的阿霉素浓度降至约50%，由于尿液产生，给药2小时结束时尿液中的阿霉素浓度进一步降低6倍。治疗结束时多柔比星的平均回收率为88.3%，在随后的4小时内额外回收率为3.7%。尿液pH值（范围5.5 - 8.5）不影响多柔比星的稳定性和全身吸收。总之，我们发现膀胱内阿霉素治疗对阿霉素的全身暴露不显著，最高的全身吸收发生在手术后不久，有高靶点（膀胱组织）特异性、阿霉素的不显著代谢和/或降解以及尿阿霉素浓度的稀释，因此，由于残余尿和尿液产生，减少肿瘤对药物的暴露。
The urine and plasma pharmacokinetics of intravesical doxorubicin were studied in 8 patients with a history of superficial bladder cancer. Patients received 6 weekly treatments of 40 mg. doxorubicin in 20 ml. physiological saline. Doxorubicin was detectable (0.2 ng./ml. or more) in plasma from 6 of 8 patients during the initial treatment. The maximal concentrations ranged from 0.5 to 4.5 ng./ml. (mean 1.4). Doxorubicin was not detected in plasma from 7 of 8 patients during treatment 2 and not detected in any patient during treatment 4. The doxorubicin concentrations in urine decreased to approximately 50% at 5 minutes after dosing due to dilution by post-catheterization residual urine, and decreased by a further 6-fold by the end of the 2-hour treatment due to urine production. The recovery of doxorubicin at the end of treatment averaged 88.3%, with an additional recovery of 3.7% during the subsequent 4 hours. Urinary pH (range 5.5 to 8.5) did not affect the stability nor the systemic absorption of doxorubicin. In conclusion, we found that for intravesical doxorubicin therapy there was insignificant systemic exposure to doxorubicin, the highest systemic absorption from the bladder occurred shortly after surgery, there was high target site (bladder tissue) specificity, insignificant metabolism and/or degradation of doxorubicin, and dilution of urinary doxorubicin concentrations and, therefore, decreased tumor exposure to the drug due to residual urine and urine production.