The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin, substrate of organic anion-transporting polypeptide 1B1.
The aim of this study was to explore potential herb-drug interaction between baicalin and rosuvastatin, a typical substrate for organic anion-transporting polypeptide 1B1 (OATP1B1) related to different OATP1B1 haplotype groups. Eighteen unrelated healthy volunteers who were CYP2C9*1/*1 with different OATP1B1 haplotypes (six OATP1B1*1b/*1b, six OATP1B1*1b/*15, and six OATP1B1*15/*15) were selected to participate in this study. Rosuvastatin (20 mg orally) pharmacokinetics after coadministration of placebo and 50-mg baicalin tablets (three times daily orally for 14 days) were measured for up to 72 h by liquid chromatography-mass spectrometry in a two-phase randomized crossover study. After baicalin treatment, the area under the plasma concentration-time curve (AUC)(0-72) and AUC(0-infinity) of rosuvastatin decreased by 47.0+/-11.0% (P=0.001) and 41.9+/-7.19% (P=0.001) in OATP1B1*1b/*1b, 21.0+/-20.6% (P=0.035) and 23.9+/-8.66% (P=0.004) in OATP1B1*1b/*15, and 9.20+/-11.6% (P=0.077) and 1.76+/-4.89% (P=0.36) in OATP1B1*15/*15, respectively. Moreover, decreases of both AUC(0-72) and AUC(0-infinity) of rosuvastatin among different haplotype groups were significantly different (P=0.002 and <0.001). Baicalin reduces plasma concentrations of rosuvastatin in an OATP1B1 haplotype-dependent manner.
Fan
L
L
Pharmacogenetics Research Institute, Central South University, Changsha, Hunan, People's Republic of China.
Zhang
W
W
Guo
D
D
Tan
Z-R
ZR
Xu
P
P
Li
Q
Q
Liu
Y-Z
YZ
Zhang
L
L
He
T-Y
TY
Hu
D-L
DL
Wang
D
D
Zhou
H-H
HH
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology*; D005464:Fluorobenzenes / Q000097:blood / Q000493:pharmacokinetics*; D006239:Haplotypes / Q000502:physiology; D029001:Herbal Medicine; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D028321:Plant Preparations / Q000494:pharmacology*; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D000068718:Rosuvastatin Calcium; D013379:Substrate Specificity / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics*
D005419:Flavonoids; D005464:Fluorobenzenes; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D028321:Plant Preparations; D011743:Pyrimidines; C503999:SLCO1B1 protein, human; D013449:Sulfonamides; C038044:baicalin; D000068718:Rosuvastatin Calcium