Cinnamic acid in rabbits Pharmacokinetic and pharmacodynamic studies
Pharmacokinetic and pharmacodynamic study of cinnamic acid in rabbits
Abstract
Cinnamic acid (cinnamic acid; CA) is a rich in natural substances in plants and present in the benzoin, Styrax and other Chinese
medicinal herbs. CA in addition to antimicrobial and inhibit tumor cell proliferation effect, there anticoagulant activity. But CA
pharmacokinetics and pharmacodynamic still no complete information is available, this study aims to probe CA in rabbits Pharmacokinetic and pharmacodynamic properties of the association between them, but also for The main metabolite
hippuric acid (hippuric acid; HA) of the generation and pharmacokinetic properties to be explored.
Determination of HPLC analysis method using plasma
concentrations of CA and HA content, use the backward column with UV detection wavelengths were set at 270nm and 225nm. CA
calibration standard line levels between 0.012 to 50 micrograms per milliliter between the good linearity, and back to back within
analysis coefficients of variation were between less than 10%. CA yield rate 84.53%, HA yield rate 83.62%, indicating that this method is a good plasma Inspection CA and HA detection.
In the stability test, at room temperature (25 ℃), within seven days, CA and HA in the pH2 ~ 3 in the buffer solution has good stability, but to alkaline pH or buffer solution is produced degradation, so
acidification Inspection and quantitative accuracy is the preservation of the necessary steps.
Six male New Zealand white rabbits were given intravenous
injection of CA 25, 50, 75 and 100 mg / kg, oral administration of 75 mg / kg, and intraperitoneal injection of 50 mg / kg. CA showed two-
compartment intravenous pharmacokinetic properties, the
elimination half life was 91.0 ± 7.6 (25 mg / kg), 99.5 ± 19.7 (50 mg / kg),
96.6 ± 19.4 (75 mg / kg) minutes; Clear rates were 0.0822 ± 0.0086 (25 mg / kg), 0.0849 ± 0.0271 (50 mg / kg), 0.0890 ± 0.0195 (75 mg / kg) L / min. The intravenous injection of 100 mg / kg, the compartment was also found, but the distribution and elimination rate of 25 ~ 75 mg / kg when there are significant differences in the pharmacokinetics were linear. The intravenous injection of 25 ~ 75 mg / kg of CA generated by the plasma concentration of HA and other area under the curve of HA-Na molar to vote and after the intravenous injection means income compared to the ratio of HA generated by CA was 40.18 ± 5.23 %.
In the rabbit oral CA 75 mg / kg after, Tmax appears in the 4.7 ± 1.5 min, and the dosage of intravenous injection area under the curve compared with its oral administration obtained the absolute
bioavailability was 0.24 ± 0.02, show that oral , the first-pass effect large. The vote by intraperitoneal injection with CA 50 mg / kg in rabbits with intravenous doses with other area under the curve compared to obtain the intraperitoneal injection of absolute
bioavailability was 0.91 ± 0.04, shows good absorption rate CA and liver first-pass effect of about 9 ± 4%, therefore, CA low oral
availability, should be mainly affected by the decomposition of the gastrointestinal tract.
Bleeding after the test to give CA time (BT), prothrombin time (PT), activated thromboplastin time part (aPTT) of three hours to explore the pharmacodynamics of CA's anti-clotting properties. Intravenous injection in rabbits 75, 100 mg / kg of CA after, BT, PT, aPTT clotting time were prolonged, while the intravenous injection of 25 ~ 100 mg / kg and oral 75 mg / kg after, PT were significant extension of the phenomenon, known CA in rabbits and inhibition of anticoagulant effect and a common means of external means of coagulation factors and platelet aggregation effects.
CA and HA of the drug concentration in blood clotting time of change with no direct relevance. Try to use to link the average blood levels of CA pharmacokinetic and pharmacodynamic
properties, when the average blood levels of CA, respectively, 5.73 ± 1.07, 7.49 ± 0.13, 17.53 ± 2.43 ug / ml, the coagulation test PT, BT, aPTT
time can be observed in a significant extension of the phenomenon.
The dose linear pharmacokinetics, the role of anticoagulation efficacy and the average blood levels of CA plot, known CA
pharmacokinetics and pharmacodynamics between the existence of hysteresis (hysteresis), or after administration Although up to the same average blood levels, but only at a later point in time observed significant anticoagulant effect.
