Hydrochloride Harmine Capsule In Vivo Pharmacokinetic Study

Harmine hydrochloride capsule is a new antitumor and antihydatid disease drug which was prepared using effective alkaloid ingredient extracted from pegnamum harmala seeds. In order to provide scientific basis for the development of this new drug, a series of experiments had been done on the pharmacokinetics in various animals. The tissue distribution and accumulation characteristics after oral administration were also studied in mice. So far, this study has not been found in recent literatures home and abroad. In the experimental studies on the process of harmine hydrochloride capsule in vivo, the pharmacokinetics of oral administration harmine hydrochloride capsule were compared with intravenous injection harmine hydrochloride solution in rabbits, rats, and mice by cross test design. We also studied the tissue distribution and accumulation characteristics after ig 40mg/kg of harmine hydrochloride to mice. Serum and tissue concentration of harmine hydrochloride were determined using RP-HPLC. The chromatographic conditions were optimized with a reversed-phase column (C18)using methonal ?.O1M ammonium sulphate buffer (70:30) as the mobile phase at a flow rate of lmllmin, column temperature of 40 慍, and detector wavelength of 320nm, flowing an injection of lOpJ. Calculation of concentration was done by using a suitable calibration curve: C(pg/ml)= 2.9O5AhIAs + 0.1702 (r~0.9998) .The calibration graph was linear for 0.l拁l0~ g/ml of harmine hydrochloride. The mean recovery of harmine hydrochloride in plasma was 99.85 ?2.34%, RSD=2.34%. The precision and reappearance of harmine hydrochloride meet the requirements. The mean recovery of harmine hydrochloride in liver, kidney, brain, lung, heart, plasma, muscle, stomach, intestines, thymus, spleen, and fat were 96.57?.72.. 103.5?.98.. 98.27?.28.. 98.37 ?.97.. 105.8?.91.. 103.4?.87 106.0?.05.. 99.43 ?.28.. 101.6 ?.47.. 103.3?.41.. 96.16?.69 and 98.03?.59% ,respectively. The results of the pharmacokinetic test indicated that the plasma concentration梩ime curves after po or iv harmine hydrochloride were fitted to two compartments open model in rabbits, rats, and mice. The results of pharmacokinetic test of harmine hydrochloride capsule in rabbits after oral administration showed that the main parameters of the highest plasma concentration (C~), peak time (T,~), the half life of absorption (tip~a), the half life of distribution (t1,2 ), and the half life of elimination (t1~ ~) were 1.541?1 .52~tg/m1, 0.697 8 ? 0.635h, 0.2873 睉0.338h, 0.7160 ?0.426h, and 4.389 ?1.59h, respectively. The main parameters of t1,2 ,and t1~ ~ after injection of vein in rabbits were 0.3087?.075, and 3.337?.628b, respectively. There were no significantly difference on the main parameters of t112 ,and t112 ~ between oral and injection of vein administration in rabbits (p>0.O5). The bioavaliability of harmine hydrochloride capsule was 17.14%. The results of pharmacokinetic test of harmine hydrochloride capsule in rats after oral administration showed that the main parameters of C~, T~, tt/2ka, t~p a, ~112~ were 2.958? . 46p.g/ml, 0.2330 ?0. 130h, 0.0748 ?0.033h, 0.4208 ?0.71 lh, and 5.330 ?1 .99h, respectively. The main parameters of t1,~0 ,and t1,~ ~ after injection of vein in rats were 0.2770?0.064h, and 3.266 ?1 .83h, respectively. There were no significantly difference on the main parameters of t112 ,and t1,~ ~, between oral and inject...