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Effect of Angelica Decoction on the Pharmacokinetics of Levonorgestrel in Healthy Chinese Volunteers

Author: JiangSong
Tutor: LiHuanDe
School: Central South University
Course: Drug analysis
Keywords: Angelica decoction Levonorgestrel Pharmacokinetic Drug Interactions CYP3A4
CLC: R96
Type: Master's thesis
Year: 2011
Downloads: 27
Quote: 0
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Abstract


The purpose of this test is designed to research exists affected Angelica decoction in vivo pharmacokinetics of oral contraceptives, levonorgestrel process. Whether there is the potential interaction between the visits of Angelica and oral contraceptives levonorgestrel. Second, the method 1. Administration method of this study is a randomized, open, two-period crossover trial. 10 healthy volunteers were randomly divided into A, B groups. First cycle: A group for taking Angelica decoction seven days, eight days after taking Angelica decoction oral 1.5 mg levonorgestrel, blood was collected at set time points; B in group A at the same time in eight days oral administration of 1.5 mg levonorgestrel, blood was collected at set time points. The washout period of eight days. Second cycle: A, B two groups exchanged administration order, the same way as the first cycle. 2. Biological sample collection, and determination of levonorgestrel blood samples, respectively, in the trial of levonorgestrel medication in the morning and after taking the 20 min, 40min, 1h, 1.5h, 2h, 3h, 5h, 8h, 12h, 24h , 36h, 48h venous sampling 5 mL. Set heparin tubes, centrifuged plasma, saved to the determination of the set at -70 ℃. HPLC-MS/MS method for the determination of plasma concentration of levonorgestrel. 3. Monitoring of adverse reactions after taking levonorgestrel tablets for 2 h, 24 h and 48 h, respectively, to monitor respiration, blood pressure, body temperature, heart rate and record adverse reactions. Results 1. Levonorgestrel content determination of levonorgestrel good linear relationship in the concentration range of 0.30 ~ 20.00 ng · mL-1, the minimum detectable concentration 0.30ng · mL-1. Extraction recovery was more than 86.74%, and recoveries of between 95.30% to 107.25%, intra-day RSD less than 11.25%, low, medium, and high concentration of quality control samples are stable concentration variation of less than 6.76 %. Pharmacokinetic study after a single oral dose of 1.5mg levonorgestrel tablets 10 healthy subjects after a single oral dose of levonorgestrel tablets, levonorgestrel pharmacokinetic parameters Cmax of Tmax, T1 / 2, CL / F, and MRT were 44.03 ± 17.71 ng h-mL-1, 54.20 ± 23.71 ng-h-mL-1, 14.15 ± 5.15 ng-mL-1, 2.33 ± 1.36h, 4.82 ± 1.47h , 227.04 ± 117.39mL · h-1 and 4.05 ± 1.54h. Angelica decoction on the pharmacokinetics of levonorgestrel taking Angelica decoction group not taking Angelica decoction group compared to the AUC reducing 21.6%, a 31.2% reduction in Cmax of Tmax did not change significantly, T1 / 2 shortened by 35.4%, CL / F increased by 42.7%, from a statistical point of analysis of the above data was no statistically significant difference in the two-week period. Experimental results show that there are large individual differences in body pharmacokinetics of levonorgestrel, individual differences and the small sample size also may be caused no statistically significant difference. 4 adverse reactions during the test, there was no any adverse reactions occur. Conclusion Angelica decoction can reduce the bioavailability of levonorgestrel in healthy humans, but no statistical significance. The experiment found that there are individual differences in the pharmacokinetics of levonorgestrel process.

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