The enhancing effect of borneol on the absorption of tetramethylpyrazine / 药学学报

ABSTRACT

To explore the mechanism of the absorption enhancement of borneol, the effect of borneol on the intestinal absorption and the pharmacokinetics of tetramethylpyrazine phosphate after oral administration were investigated. In situ intestinal recirculation was performed to study the effect of various concentrations of borneol on the absorption of tetramethylpyrazine phosphate at duodenum, jejunum, ileum and colon. After oral administration of tetramethylpyrazine phosphate, the mixture of tetramethylpyrazine phosphate and borneol and the mixture of tetramethylpyrazine phosphate and verapamil in rats, the concentrations of tetramethylpyrazine phosphate in plasma were determined by RP-HPLC at predesigned time. The pharmacokinetic parameters were compared based on the results of the three animal experiments, and analyzed with software program 3p97. The result showed that tetramethylpyrazine phosphate could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows colon > duodenum > jejunum > ileum, but without saturation, which demonstrated that tetramethylpyrazine phosphate was absorbed via simple diffusion. Borneol could enhance the intestinal absorption of tetramethylpyrazine phosphate, however, not in proportion. There was no obvious difference between the test group and the control group when 10 microg x mL(-1) borneol was added (P > 0.05), while when the concentration comes to 25 microg x mL(-1) and 50 microg x mL(-1), significant differences were observed (P < 0.05). Borneol and verapamil did enhance the bioavailability of tetramethylpyrazine phosphate after oral administration in rats. The enhancing effect of borneol showed only when the concentration came to a certain level but with no specific sites existed in the intestine. One of the mechanisms of borneol on the enhancing effect on absorption of tetramethylpyrazine phosphate might be the inhibition of the metabolism of CYP 3A and exocytosis of P-gp.