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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

The study design for the drug administration. 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.
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fig1: The study design for the drug administration. 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.

Mentions: In this study, the dose was calculated using a formula for dose translation from humans to rats. This formula uses the body surface area normalization method to convert the dose from humans to rats [15]. In clinical therapy, the dosage of 5-FU was 600 mg/m2, for the initial treatment and maintenance therapy. Using the formula, the human equivalent dosage of 5-FU in rats is 100 mg/kg. A previous study revealed that, comparing the dose-normalized area under the curve (AUC) at different intravenous doses of 5-FU in rats, the dose-normalized AUC after the administration of 100 mg/kg is greater than 50 mg/kg, or 10 mg/kg [16], so 100 mg/kg was chosen as a suitable 5-FU dose for rats to determine the 5-FU pharmacokinetic parameters. The extract powder of JWXYS was dissolved in deionized water at a concentration of 100 mg/mL, for oral administration by gavages to the rats. A daily dose of JWXYS extract for humans is 5.8 g once a day for adults. This equates to 600 mg/kg/day for rats and this dosage is called a daily dose in this study. However, the dose of JWXYS depends on the symptoms, so a double dose (1200 mg/kg/day) and a high dose (2400 mg/kg/day) of JWXYS were also used to determine the herb-drug interaction in detail. Rats in group 1 were initially anesthetized using an anesthetic mixture (10 mL/kg, i.p.) of urethane (1 g/kg) and α-chloralose (0.01 g/mL) and were then given 5-FU (100 mg/kg, i.v.) alone through the femoral vein. Groups 2–4 were pretreated with different doses of JWXYS for 5 consecutive days and on the 5th day, 1 h after pretreatment with JWXYS, the rats were anesthetized with the anesthetic mixture (10 mL/kg, i.p.) to perform surgery and another 1 h was taken to balance the microdialysis device after the animal experiment concluded. 5-FU (100 mg/kg, i.v.) was finally injected into the femoral vein. The administration protocol was shown in Figure 1.


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)

The study design for the drug administration. 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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: The study design for the drug administration. 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.
Mentions: In this study, the dose was calculated using a formula for dose translation from humans to rats. This formula uses the body surface area normalization method to convert the dose from humans to rats [15]. In clinical therapy, the dosage of 5-FU was 600 mg/m2, for the initial treatment and maintenance therapy. Using the formula, the human equivalent dosage of 5-FU in rats is 100 mg/kg. A previous study revealed that, comparing the dose-normalized area under the curve (AUC) at different intravenous doses of 5-FU in rats, the dose-normalized AUC after the administration of 100 mg/kg is greater than 50 mg/kg, or 10 mg/kg [16], so 100 mg/kg was chosen as a suitable 5-FU dose for rats to determine the 5-FU pharmacokinetic parameters. The extract powder of JWXYS was dissolved in deionized water at a concentration of 100 mg/mL, for oral administration by gavages to the rats. A daily dose of JWXYS extract for humans is 5.8 g once a day for adults. This equates to 600 mg/kg/day for rats and this dosage is called a daily dose in this study. However, the dose of JWXYS depends on the symptoms, so a double dose (1200 mg/kg/day) and a high dose (2400 mg/kg/day) of JWXYS were also used to determine the herb-drug interaction in detail. Rats in group 1 were initially anesthetized using an anesthetic mixture (10 mL/kg, i.p.) of urethane (1 g/kg) and α-chloralose (0.01 g/mL) and were then given 5-FU (100 mg/kg, i.v.) alone through the femoral vein. Groups 2–4 were pretreated with different doses of JWXYS for 5 consecutive days and on the 5th day, 1 h after pretreatment with JWXYS, the rats were anesthetized with the anesthetic mixture (10 mL/kg, i.p.) to perform surgery and another 1 h was taken to balance the microdialysis device after the animal experiment concluded. 5-FU (100 mg/kg, i.v.) was finally injected into the femoral vein. The administration protocol was shown in Figure 1.

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