Naitoh Hiroyuki, Kawaguch Akira, Yamamoto Hiroshi, Mekata Eiji, Tan Tohru, Morii Hiroaki, Chiba Mikio
Dept of Surgery, Shiga University of Medical Science.
Gan To Kagaku Ryoho. 2004 Nov;31(12):2031-4.
We measured docetaxel (TXT) concentrations in the blood and ascites after drip infusion into each vessel and intraperitoneal cavity of a patient with advanced gastric cancer. The peak concentration was reached immediately (first time 244 ng/ml, second time 215 ng/ml) after the infusion of TXT (25 mg/m2) into the vessels. The concentration of TXT for ascites peaked after 30 min of drip infusion (first time 26 ng/ml, second time 30 ng/ml). AUC ascites/AUC blood was 27.2% and 35.8% respectively. This is the first report demonstrating the concentration of TXT in ascites after drip infusion into vessels. When TXT was administered into the peritoneal cavity, the peak concentration of ascites was reached immediately (54,200 ng/ml). After 240 min, the TXT concentration in the peritoneal cavity was still high (14,200 ng/ml). In blood, the level peaked (64 ng/ml) at 120 min. After 240 min, the TXT level in the blood remained 44 ng/ml. AUC blood/AUC ascites was only 0.25%. These results suggested that the transition rate of TXT from blood to intraperitoneal cavity was excellent, and that TXT was suitable for the treatment of peritoneal dissemination of gastric cancer. Furthermore, infusion of TXT (25 mg/m2) into the peritoneal cavity may directly and systemically provide its antitumor effect. If we prefer the antitumor effect directly, a much lower dose infusion of TXT may be recommended.
我们测量了晚期胃癌患者经每条血管及腹腔滴注多西他赛（TXT）后血液和腹水中的多西他赛浓度。向血管内滴注多西他赛（25mg/m²）后，浓度立即达到峰值（第一次244ng/ml，第二次215ng/ml）。向腹水中滴注多西他赛后30分钟，TXT浓度达到峰值（第一次26ng/ml，第二次30ng/ml）。腹水与血液的AUC比值分别为27.2%和35.8%。这是首次报道血管滴注后腹水中TXT的浓度情况。当向腹腔内给药TXT时，腹水的峰值浓度立即达到（54200ng/ml）。240分钟后，腹腔内的TXT浓度仍然很高（14200ng/ml）。血液中，在120分钟时达到峰值（64ng/ml）。240分钟后，血液中的TXT水平仍为44ng/ml。血液与腹水的AUC比值仅为0.25%。这些结果表明，TXT从血液向腹腔的转移率极佳，且TXT适用于治疗胃癌腹膜转移。此外，向腹腔内滴注TXT（25mg/m²）可直接且全身性地发挥其抗肿瘤作用。如果我们更倾向于直接的抗肿瘤作用，可能推荐更低剂量的TXT滴注。
