Pharmacokinetic study of MMC in the hyperthermic perfusion chemotherapy
Author(s): WANG Bin, CUI Shu-zhong, LEI Ming, YANG Jian-an, LI Jin, Department of Urology, Cancer Center of Guangzhou Medical University, Intracelom Hyperthermic Perfusion Therapy Center, Cancer Center of Guangzhou Medical University
Pages: 889-892
Year: 2015 Issue: 7
Journal: Journal of Tropical Medicine
Keyword: bladder cancer; local hyperthermia; chemotherapy; pharmacokinetic study;
Abstract: Objective To provide the pharmacokinetic studies on hyperthermic perfusion chemotherapy(HIVEC), the MMC concentration in the plasma and perfusion fluid at different time points were observed. Methods 6 patients suffering from UCC received HIVEC with MMC were enrolled. Plasma samples and perfusion fluid 3 ~5 ml were obtained at different time points during HIVEC. The samples were placed into the refrigerator for 3 hours, and then centrifuged at 4℃, 1 500 r / min for 10 minutes. The samples were placed in-80℃ refrigerator. Perfusion fluid and serum samples were analyzed with high performance liquid chromatography(HPLC) using Hypersil ODS2(4.6 mm×250 mm, 5 μm) column, colonial spirit-water(V ∶ V = 35 ∶ 65)and 365 nm UV detection. DAS2.0 software was used to calculate the pharmacokinetic parameters. Results The standard plasma concentration as the abscissa(x), and the MMC peak area as the ordinate(y) for linear regression, the resulting linear equation was y=bx+a: y=0.0108(±0.0001)x+0.005(±0.003),r=0.999. From the concentration of MMC in the plasma,we can draw the time-concentration curves. And the area under the curves was 187(167~468) ng /(ml·min). The plasma MMC concentration in 0 min, 15 min, 30 min, 45 min, 60 min, 2 h, 4 h and 6 h were(3.25 ±3.34)ng / ml,(4.57 ±3.82)ng / ml,(5.23 ±3.43)ng / ml,(7.65 ±6.24)ng / ml,(7.57 ±5.30)ng / ml,(5.06 ±3.82)ng / ml,(4.52 ±3.42)ng / ml and(3.28 ±3.18)ng / ml,respectively.The peak was in 45~60 min, which reached to plateau. The perfusion fluid MMC concentration in 0, 15, 30 and 45 min were(0.085 ±0.021)mg / ml,(0.073 ±0.018)mg / ml,(0.068 ±0.020)mg / ml and(0.065 ±0.016) mg / ml, respectively.Conclusion The highest MMC plasma concentration was well below the threshold concentration(400 ng / ml) generally assumed for risk of myelosuppression. The perfusion fluid MMC concentration was high and steady during the HIVEC procedure.
Pages: 889-892
Year: 2015 Issue: 7
Journal: Journal of Tropical Medicine
Keyword: bladder cancer; local hyperthermia; chemotherapy; pharmacokinetic study;
Abstract: Objective To provide the pharmacokinetic studies on hyperthermic perfusion chemotherapy(HIVEC), the MMC concentration in the plasma and perfusion fluid at different time points were observed. Methods 6 patients suffering from UCC received HIVEC with MMC were enrolled. Plasma samples and perfusion fluid 3 ~5 ml were obtained at different time points during HIVEC. The samples were placed into the refrigerator for 3 hours, and then centrifuged at 4℃, 1 500 r / min for 10 minutes. The samples were placed in-80℃ refrigerator. Perfusion fluid and serum samples were analyzed with high performance liquid chromatography(HPLC) using Hypersil ODS2(4.6 mm×250 mm, 5 μm) column, colonial spirit-water(V ∶ V = 35 ∶ 65)and 365 nm UV detection. DAS2.0 software was used to calculate the pharmacokinetic parameters. Results The standard plasma concentration as the abscissa(x), and the MMC peak area as the ordinate(y) for linear regression, the resulting linear equation was y=bx+a: y=0.0108(±0.0001)x+0.005(±0.003),r=0.999. From the concentration of MMC in the plasma,we can draw the time-concentration curves. And the area under the curves was 187(167~468) ng /(ml·min). The plasma MMC concentration in 0 min, 15 min, 30 min, 45 min, 60 min, 2 h, 4 h and 6 h were(3.25 ±3.34)ng / ml,(4.57 ±3.82)ng / ml,(5.23 ±3.43)ng / ml,(7.65 ±6.24)ng / ml,(7.57 ±5.30)ng / ml,(5.06 ±3.82)ng / ml,(4.52 ±3.42)ng / ml and(3.28 ±3.18)ng / ml,respectively.The peak was in 45~60 min, which reached to plateau. The perfusion fluid MMC concentration in 0, 15, 30 and 45 min were(0.085 ±0.021)mg / ml,(0.073 ±0.018)mg / ml,(0.068 ±0.020)mg / ml and(0.065 ±0.016) mg / ml, respectively.Conclusion The highest MMC plasma concentration was well below the threshold concentration(400 ng / ml) generally assumed for risk of myelosuppression. The perfusion fluid MMC concentration was high and steady during the HIVEC procedure.
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