Effect of ferulic acid on the brain pharmacokinetics of tetramethylpyrazine in conscious rats.

1. In traditional Chinese medicine, Angelica sinensis is often coprescribed with Ligusticum chuanxiong Hort for the treatment of ischemic cerebrovascular diseases. Tetramethylpyrazine (TMP) is one of the most important active ingredients isolated from Ligusticum chuanxiong Hort; ferulic acid (FA) is the main water-soluble component of Angelica sinensis. 2. The purpose of this study is to investigate the possible effect of FA on the brain pharmacokinetics of TMP in conscious Sprague-Dawley rats. The pharmacokinetic parameters of TMP were investigated in brain microdialysates after oral and intravenous administration of TMP (4 mg/kg) to rats in the absence and presence of FA (5 mg/kg). Samples were collected at timed intervals for the measurement of TMP by a rapid and sensitive UPLC-MS/MS method. 3. The pharmacokinetic parameters were calculated by noncompartmental analysis for brain microdialysates. The brain pharmacokinetic data for TMP showed significant increases in C(max,)t(1/2,) AUC(0-inf) and MRT0-inf after combination with FA. After intragastric administration with FA, there were significant decreases in the T-max (from 38.33 +/- 5.77 to 21 +/- 5.48 min; p < 0.01) of TMP. This study indicated that potential drug-drug interaction between TMP and FA should be taken into consideration and the combined administration is beneficial in improving the bioavailability of TMP in the brain.