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Disposition kinetics of taxanes in peritoneal dissemination.

Miyamoto K, Shimada T, Sawamoto K, Sai Y, Yonemura Y - Gastroenterol Res Pract (2012)

Bottom Line: Taxane anticancer drugs are used to treat gastric cancer patients with peritoneal dissemination.They are administered as micellar preparations, Taxol and Taxotere, which consist of paclitaxel in Cremophor EL (crEL) and docetaxel in Polysorbate-80 (PS-80), respectively.In this paper we review the disposition kinetics of taxane anticancer drugs after intraperitoneal administration in peritoneal dissemination patients and animal models and also discuss the effect of the surfactant vehicle on the behavior of taxanes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

ABSTRACT
Treatment of cancers in the abdominal cavity, such as peritoneal dissemination, is difficult, but in principle intraperitoneal administration of anticancer drugs is expected to be preferable to systemic administration. Taxane anticancer drugs are used to treat gastric cancer patients with peritoneal dissemination. They are administered as micellar preparations, Taxol and Taxotere, which consist of paclitaxel in Cremophor EL (crEL) and docetaxel in Polysorbate-80 (PS-80), respectively. In this paper we review the disposition kinetics of taxane anticancer drugs after intraperitoneal administration in peritoneal dissemination patients and animal models and also discuss the effect of the surfactant vehicle on the behavior of taxanes.

No MeSH data available.


Related in: MedlinePlus

Values of apparent solid tumor to plasma concentration ratio (Kp, app) of paclitaxel and docetaxel 1 h after an i.p. (40 mg/kg, open column) or i.v. (5 mg/kg, closed column) injection of Taxol and Taxotere into AH130 tumor-bearing rats [15]. Each column with bar represents the mean ± SD of three rats. *Significantly different from docetaxel at P < 0.05.
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fig5: Values of apparent solid tumor to plasma concentration ratio (Kp, app) of paclitaxel and docetaxel 1 h after an i.p. (40 mg/kg, open column) or i.v. (5 mg/kg, closed column) injection of Taxol and Taxotere into AH130 tumor-bearing rats [15]. Each column with bar represents the mean ± SD of three rats. *Significantly different from docetaxel at P < 0.05.

Mentions: After i.p. administration of taxanes, the ascitic concentration of paclitaxel decayed very slowly, whereas that of docetaxel decreased rapidly. The plasma concentrations of both drugs were very low, but that of paclitaxel increased until 4 h and then remained at a plateau, while that of docetaxel reached the maximum at 1.5 h and then decreased (Figure 3). The values of AUCp, 0–24 h, and AUCa, 0–24 h of paclitaxel were significantly larger, by about 2- and 6-fold, respectively, than those of docetaxel, and the apparent first-order absorption rate constant from the peritoneal cavity (ka) of paclitaxel was extremely small (Table 2). The AUCa/AUCp ratio of paclitaxel was much larger than that of docetaxel. These results indicate that paclitaxel was retained at much higher concentration than docetaxel in the peritoneal cavity after i.p. administration of taxane preparations, and the transfer of paclitaxel into the systemic circulation was much lower than that of docetaxel, in agreement with clinical findings [7, 10–13]. Figure 4 shows the changes of taxane concentration in free cancer cells in the peritoneal cavity after i.p. administration of Taxol and Taxotere (each 40 mg/kg). The concentration of paclitaxel was very low after Taxol administration, while that of docetaxel was high just after Taxotere administration and then decreased gradually in parallel with the decay of the peritoneal concentration. On the other hand, at 1 h after i.p. administration, the concentration of paclitaxel in solid cancer tissue growing in the peritoneum (1.3 ± 0.2 μg/g tissue) was lower than that of docetaxel (4.1 ± 2.8 μg/g tissue). Figure 5 shows the apparent concentration ratio in solid cancer tissue versus plasma (Kp, app) 1 h after i.p. or i.v. administration. No marked difference was observed between the Kp,app values of these drugs after i.p. administration, but after i.v. administration the Kp, app of paclitaxel was significantly smaller than that of docetaxel. These results indicate that after i.p. administration of Taxol, paclitaxel was retained at high concentration in the peritoneal cavity and was not readily transferred into either the systemic circulation or cancer cells and tissues. The distribution of paclitaxel into cancer tissues was also low after i.v. administration. Docetaxel was more extensively distributed into cancer tissues than paclitaxel after administration via both routes.


Disposition kinetics of taxanes in peritoneal dissemination.

Miyamoto K, Shimada T, Sawamoto K, Sai Y, Yonemura Y - Gastroenterol Res Pract (2012)

Values of apparent solid tumor to plasma concentration ratio (Kp, app) of paclitaxel and docetaxel 1 h after an i.p. (40 mg/kg, open column) or i.v. (5 mg/kg, closed column) injection of Taxol and Taxotere into AH130 tumor-bearing rats [15]. Each column with bar represents the mean ± SD of three rats. *Significantly different from docetaxel at P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3362138&req=5

fig5: Values of apparent solid tumor to plasma concentration ratio (Kp, app) of paclitaxel and docetaxel 1 h after an i.p. (40 mg/kg, open column) or i.v. (5 mg/kg, closed column) injection of Taxol and Taxotere into AH130 tumor-bearing rats [15]. Each column with bar represents the mean ± SD of three rats. *Significantly different from docetaxel at P < 0.05.
Mentions: After i.p. administration of taxanes, the ascitic concentration of paclitaxel decayed very slowly, whereas that of docetaxel decreased rapidly. The plasma concentrations of both drugs were very low, but that of paclitaxel increased until 4 h and then remained at a plateau, while that of docetaxel reached the maximum at 1.5 h and then decreased (Figure 3). The values of AUCp, 0–24 h, and AUCa, 0–24 h of paclitaxel were significantly larger, by about 2- and 6-fold, respectively, than those of docetaxel, and the apparent first-order absorption rate constant from the peritoneal cavity (ka) of paclitaxel was extremely small (Table 2). The AUCa/AUCp ratio of paclitaxel was much larger than that of docetaxel. These results indicate that paclitaxel was retained at much higher concentration than docetaxel in the peritoneal cavity after i.p. administration of taxane preparations, and the transfer of paclitaxel into the systemic circulation was much lower than that of docetaxel, in agreement with clinical findings [7, 10–13]. Figure 4 shows the changes of taxane concentration in free cancer cells in the peritoneal cavity after i.p. administration of Taxol and Taxotere (each 40 mg/kg). The concentration of paclitaxel was very low after Taxol administration, while that of docetaxel was high just after Taxotere administration and then decreased gradually in parallel with the decay of the peritoneal concentration. On the other hand, at 1 h after i.p. administration, the concentration of paclitaxel in solid cancer tissue growing in the peritoneum (1.3 ± 0.2 μg/g tissue) was lower than that of docetaxel (4.1 ± 2.8 μg/g tissue). Figure 5 shows the apparent concentration ratio in solid cancer tissue versus plasma (Kp, app) 1 h after i.p. or i.v. administration. No marked difference was observed between the Kp,app values of these drugs after i.p. administration, but after i.v. administration the Kp, app of paclitaxel was significantly smaller than that of docetaxel. These results indicate that after i.p. administration of Taxol, paclitaxel was retained at high concentration in the peritoneal cavity and was not readily transferred into either the systemic circulation or cancer cells and tissues. The distribution of paclitaxel into cancer tissues was also low after i.v. administration. Docetaxel was more extensively distributed into cancer tissues than paclitaxel after administration via both routes.

Bottom Line: Taxane anticancer drugs are used to treat gastric cancer patients with peritoneal dissemination.They are administered as micellar preparations, Taxol and Taxotere, which consist of paclitaxel in Cremophor EL (crEL) and docetaxel in Polysorbate-80 (PS-80), respectively.In this paper we review the disposition kinetics of taxane anticancer drugs after intraperitoneal administration in peritoneal dissemination patients and animal models and also discuss the effect of the surfactant vehicle on the behavior of taxanes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

ABSTRACT
Treatment of cancers in the abdominal cavity, such as peritoneal dissemination, is difficult, but in principle intraperitoneal administration of anticancer drugs is expected to be preferable to systemic administration. Taxane anticancer drugs are used to treat gastric cancer patients with peritoneal dissemination. They are administered as micellar preparations, Taxol and Taxotere, which consist of paclitaxel in Cremophor EL (crEL) and docetaxel in Polysorbate-80 (PS-80), respectively. In this paper we review the disposition kinetics of taxane anticancer drugs after intraperitoneal administration in peritoneal dissemination patients and animal models and also discuss the effect of the surfactant vehicle on the behavior of taxanes.

No MeSH data available.


Related in: MedlinePlus