| Doxazosin Mesylate (abbreviated to DM) , a quinazoline derivative with a 1-adrenoceptor antagonistic activity , is a first-line therapeutic agent for hypertension,particularly for hypertension with CHD (coronary heart disease) or renal insufficiency on a once-daily dosing regimen The combination of DM and ACE inhibitors,calcium ionic channel blockers diuretics, ~ -blockers or other medications has been found to be effective in controlling blood pressure . To investigate the influence of the combination on the pharmacokinetics of DM , the rat was selected as major object and tetrainethylpyrazine hydrochloride (TMPH) as the medication for combination , studied the pharmacokinetics of DM when in combination with TMPI-I on the base of the pharmacokinetics of DM when DM was dosed to rats alone , and revealed the influence of the combination on the pharmacokinetics of DM in rats.The high-performance liquid chromatography (HPLC) with UV detection was developed for quantifying the concentration of DM in intestine perfusing solution .~ plasma~. tissue homogenate excreta and other biological samples . The calibration curve of DM in biological sample was linear in the range from 0.100 to 100 ~?g/ml , with r> 0.9943 , and the LOQ of DM was about 1 ng . The extraction recoverise of DM and TMPH in all samples were over 90 % , the relative standard deviations of within - day and between - day of DM were lower than 7 % . This method was simple rapid and accurate enough to be used in this pharmacokinetic study.To explore the intestinal absorption characters of DM and the factors affecting absorption of DM, the changes of the absorption of DM when in combination with TMPH by utilizing the rat intestinal recirculating method in situ . The intestine absorption of DM was pH-dependant and3Abstractconcentration-dependent (PO.05) , which suggested that the intestinal absorption of DM was via the passive transport mechanism ; TMPH restrained the absorption of DM from the intestine (P |
PDF Full Text Request