Abstract
Background: Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT) is the most common traditional formula given to colorectal and breast cancer patients in Taiwan, according to a statistical study of the National Health Insurance Research Database. 5-Fluorouracil (5-FU) is widely used as the first line of treatment for colorectal cancer. Thus, the aim of study is to investigate the pharmacokinetic interaction of XSLJZT and 5-FU. Methods: To investigate the herb–drug interaction of XSLJZT with 5-FU as well as its metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) using pharmacokinetics, a high-performance liquid chromatography (HPLC) system coupled with a photodiode array detector was developed to monitor 5-FU and 5-FDHU levels in rat blood. Rats were divided into three cohorts, one of which was administered 5-FU (100 mg/kg, iv—intravenous) alone, while the other two groups were pretreated with low and high doses of XSLJZT (600 mg/kg/day or 2400 mg/kg/day for 5 consecutive days) in combination with 5-FU. Results: The results demonstrated that 5-FU level was not significantly different between the group treated with only 5-FU and the group pretreated with a normal dose of XSLJZT (600 mg/kg/day). However, pharmacokinetic analysis revealed that pretreatment with a high dose of XSLJZT (2400 mg/kg/day) extended the residence time and increased the volume of distribution of 5-FU. No significant distinctions were found in 5-FDHU pharmacokinetic parameters at three doses of XSLJZT. Conclusions: Overall, the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice.
Highlights
Use of the anti-metabolite 5-fluorouracil (5-FU) as a chemotherapeutic agent has maintained great clinical relevance since its introduction over 50 years ago
10–30% of individuals treated with 5-FU experienced a serious life-threatening adverse effect at the standard dose [3]; these tchoemseplcicoamtipolniscathioavnes hbaeveen baetetnribautttreidbuttoedthtoe thcaetacbaotalibcolpicatphawthawy aoyf o5f-5F-UFU[4[]4.].OOvevrer8855%% ooff tthhee aaddmmiinniisstteerreedd 55--FFUU ccoommppoouunndd iiss ddeeggrraaddeedd iinnttoo 55--flfluuoorroo--55,66--ddiihhyyddrroouurraacciill ((55--FFDDHHUU)) iinn tthhee lliivveerr tthhrroouugghh aacactaabtaoblioclipcatphawthawy amyedmiaetdediabteyddibhyyddroihpyydrirmopidyirnime dideihnyedrdoegheyndarsoeg(DenPaDse) [5(D,6P].DIn) a[d5,d6i]t.ioInn, 5a-dFdDitHioUn,f5o-rFmDsH5U-flfuoorrmo-su5r-efilduoo-rpor-oupreioidnoic-p(rFoUpPioAn)icac(iFdUaPnAd)αa-cfliduoarnod-βα--afllaunoirnoe-β(F-aBlaAnLin) ein(FaBtAwLo)-sitnepa rtweaoc-tsiotenp
The results reveal that the concentration versus time curves (AUC) for 5-FU in plasma are 4527 ± 974 μg/mL, 4640 ± 686 μg/mL, and 6343 ± 1272 μg/mL, following intravenous administration of the three groups, respectively
Summary
Use of the anti-metabolite 5-fluorouracil (5-FU) as a chemotherapeutic agent has maintained great clinical relevance since its introduction over 50 years ago. 10–30% of individuals treated with 5-FU experienced a serious life-threatening adverse effect at the standard dose [3]; Int. J. 10–30% of individuals treated with 5-FU experienced a serious life-threatening adverse effect at the standard dose [3]; these tchoemseplcicoamtipolniscathioavnes hbaeveen baetetnribautttreidbuttoedthtoe thcaetacbaotalibcolpicatphawthawy aoyf o5f-5F-UFU[4[]4.].OOvevrer8855%% ooff tthhee aaddmmiinniisstteerreedd 55--FFUU ccoommppoouunndd iiss ddeeggrraaddeedd iinnttoo 55--flfluuoorroo--55,,66--ddiihhyyddrroouurraacciill ((55--FFDDHHUU)) iinn tthhee lliivveerr tthhrroouugghh aacactaabtaoblioclipcatphawthawy amyedmiaetdediabteyddibhyyddroihpyydrirmopidyirnime dideihnyedrdoegheyndarsoeg(DenPaDse) [5(D,6P].DIn) a[d5,d6i]t.ioInn, 5a-dFdDitHioUn,f5o-rFmDsH5U-flfuoorrmo-su5r-efilduoo-rpor-oupreioidnoic-p(rFoUpPioAn)icac(iFdUaPnAd)αa-cfliduoarnod-βα--afllaunoirnoe-β(F-aBlaAnLin) ein(FaBtAwLo)-sitnepa rtweaoc-tsiotenp. Methods: To investigate the herb–drug interaction of XSLJZT with 5-FU as well as its metabolite 5-fluoro-5,6-dihydrouracil (5-FDHU) using pharmacokinetics, a high-performance liquid chromatography (HPLC) system coupled with a photodiode array detector was developed to monitor 5-FU and 5-FDHU levels in rat blood. Pharmacokinetic analysis revealed that pretreatment with a high dose of XSLJZT (2400 mg/kg/day) extended the residence time and increased the volume of distribution of 5-FU. Conclusions: Overall, the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice
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