Effect of sodium tanshinone II A sulfonate on the activity of CYP1A2 in healthy volunteers.
Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a famous Chinese medicine which has been used in the treatment of cardiovascular disorders for many years. Using caffeine as a probe drug, this project was designed to investigate the effect of STS on the activity of CYP1A2 in humans. Sixteen unrelated healthy volunteers were recruited for this two-phase, randomized and crossover study. The volunteers received either placebo or 60 mg day(-1) of STS injections through vein for 13 days. Pharmacokinetics of caffeine and the metabolite paraxanthine was determined by high-performance liquid chromatography. CYP1A2 activity was monitored by the ratio of paraxanthine to caffeine at 6 h in plasma. Enzyme activity analysis showed that STS significantly increased the activity of CYP1A2 by 41.1% [90% confidence interval (CI), 17.4-64.8%] (p = 0.036). The area under the curve [AUC((0-24h))] of caffeine significantly decreased by 13.3% [90% CI = 7.0-19.6%] (p = 0.005) with 13 days of treatment of STS. AUC((0-24h)) of paraxanthine significantly increased by 17.4% [90% CI = 4.3-30.5%] (p = 0.035). No significant difference was found for other parameters of caffeine and paraxanthine between two phases. STS has significantly induced the activity of CYP1A2 in vivo. Simultaneously, AUC((0-24h)) of caffeine and paraxanthine were significantly affected by STS. The findings have provided some useful information for safe and effective usage of STS in clinic.
Chen
Y
Y
Institute of Clinical Pharmacology, Hunan Medical University, Central South University, Changsha, Hunan, China.
Tu
J-H
JH
He
Y-J
YJ
Zhang
W
W
Wang
G
G
Tan
Z-R
ZR
Zhou
G
G
Fan
L
L
Zhou
H-H
HH
D000293:Adolescent; D000328:Adult; D002110:Caffeine / Q000493:pharmacokinetics; D002318:Cardiovascular Diseases; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013806:Theophylline / Q000493:pharmacokinetics; D013997:Time Factors
D010616:Phenanthrenes; D002110:Caffeine; C024894:tanshinone II A sodium sulfonate; D013806:Theophylline; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; C021183:1,7-dimethylxanthine