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Herb-drug pharmacokinetic interaction of a traditional chinese medicine jia-wei-xiao-yao-san with 5-Fluorouracil in the blood and brain of rat using microdialysis.

Chiang MH, Chang LW, Wang JW, Lin LC, Tsai TH - Evid Based Complement Alternat Med (2015)

Bottom Line: This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain.The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance.This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan.

ABSTRACT
According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days) followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

No MeSH data available.


Related in: MedlinePlus

Concentration-time curve of 5-FU in rat brain dialysate after 5-FU administration (100 mg/kg, iv) alone and pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days). Data were expressed as means ± S.E.M. (n = 6).
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fig6: Concentration-time curve of 5-FU in rat brain dialysate after 5-FU administration (100 mg/kg, iv) alone and pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days). Data were expressed as means ± S.E.M. (n = 6).

Mentions: Figure 6 shows the concentration-time curve for 5-FU in rat brain, which shows no difference between the 5-FU alone and daily and double dose of JWXYS pretreatment groups. The same phenomenon is observed in blood and the brain, where pretreatment with a high dose (2400 mg/kg/day) of JWXYS prolongs the residence time of 5-FU in the brain. In this study, 5-FU in the brain could not be detected within 150 min after 5-FU administration in the 5-FU alone and daily and double dose of JWXYS pretreatment groups, but it is observed in the high dose of JWXYS pretreatment group. The pharmacokinetic parameters of 5-FU in the brain are shown in Table 4. A daily or double dose of JWXYS has no significant effect on the AUC, Cmax⁡, t1/2, CL, or Vd. There is also no significant difference in AUC, Cmax⁡, and Vd between the 5-FU alone (894 ± 141 min μg/mL, 11.8 ± 1.8 μg/mL, and 6351 ± 953 mL/kg) and the high dose of JWXYS pretreatment group (1114 ± 128 min μg/mL, 11.2 ± 1.1 μg/mL, and 6525 ± 819 mL/kg). However, although there is no significant difference, AUC in the brain increases when 5-FU is coadministered with a high dose of JWXYS. The t1/2 value also increases significantly, from 31.9 ± 3.6 min to 47.2 ± 7.3 min, and the CL value decreases significantly, from 120 ± 23 mL/min per kg to 82.9 ± 11.0 mL/min per kg, when 5-FU is coadministered with a high dose of JWXYS.


Herb-drug pharmacokinetic interaction of a traditional chinese medicine jia-wei-xiao-yao-san with 5-Fluorouracil in the blood and brain of rat using microdialysis.

Chiang MH, Chang LW, Wang JW, Lin LC, Tsai TH - Evid Based Complement Alternat Med (2015)

Concentration-time curve of 5-FU in rat brain dialysate after 5-FU administration (100 mg/kg, iv) alone and pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days). Data were expressed as means ± S.E.M. (n = 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4377464&req=5

fig6: Concentration-time curve of 5-FU in rat brain dialysate after 5-FU administration (100 mg/kg, iv) alone and pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days). Data were expressed as means ± S.E.M. (n = 6).
Mentions: Figure 6 shows the concentration-time curve for 5-FU in rat brain, which shows no difference between the 5-FU alone and daily and double dose of JWXYS pretreatment groups. The same phenomenon is observed in blood and the brain, where pretreatment with a high dose (2400 mg/kg/day) of JWXYS prolongs the residence time of 5-FU in the brain. In this study, 5-FU in the brain could not be detected within 150 min after 5-FU administration in the 5-FU alone and daily and double dose of JWXYS pretreatment groups, but it is observed in the high dose of JWXYS pretreatment group. The pharmacokinetic parameters of 5-FU in the brain are shown in Table 4. A daily or double dose of JWXYS has no significant effect on the AUC, Cmax⁡, t1/2, CL, or Vd. There is also no significant difference in AUC, Cmax⁡, and Vd between the 5-FU alone (894 ± 141 min μg/mL, 11.8 ± 1.8 μg/mL, and 6351 ± 953 mL/kg) and the high dose of JWXYS pretreatment group (1114 ± 128 min μg/mL, 11.2 ± 1.1 μg/mL, and 6525 ± 819 mL/kg). However, although there is no significant difference, AUC in the brain increases when 5-FU is coadministered with a high dose of JWXYS. The t1/2 value also increases significantly, from 31.9 ± 3.6 min to 47.2 ± 7.3 min, and the CL value decreases significantly, from 120 ± 23 mL/min per kg to 82.9 ± 11.0 mL/min per kg, when 5-FU is coadministered with a high dose of JWXYS.

Bottom Line: This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain.The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance.This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan.

ABSTRACT
According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days) followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

No MeSH data available.


Related in: MedlinePlus