Study On The Correlation Between Pharmacokinetics And Pharmacodynamics Of Felodipine

Felodipine is one of the prefered drug of hypertension, angina pectoris on the current clinical treatment. The study was on the basis of felodipine, the plasma concentration-time of felodipine in healthy volunteers was determined by LC-MS. The pharmacokinetics of felodipine and its plasma protein binding rate were investigated in the present studies.A method for the determination of felodipine in human plasma by LC-MS is established. After adding nimodipine, the internal standard, and 100μL of 1.0 mol·L-1 NaOH solution, the plasma samples were extracted with ether:N-hexane (4:1), separated on a Kromasil C18 column(150 mm x 4.6 mm,5μm)with the mobile phase of methanol-0.1% formic acid (84:16)at the flow rate of 0.8 mL·min-1. Mass spectroscopy was equipped with an electrospray ionization(ESI) source, operated in the positive ion detector model. In selected ion monitoring(SIM)mode, the ion combinations of m/z 406 and m/z 441 was used to qualify felodipine and nimodipine respectively. The calibration curve was in good linearity over the range of 0.2-20.0 ng·mL-1 (r=0.9948).The lower limit of detection was 0.2 ng·mL-1.The recovery for felodiping was more than 81.9%.within-day and between-day RSDs were less than 14.9%.This method is accurate, sensitive for determination of felodipine in human plasma and to study its pharmacokinetics.The equilibrium dialysis to determine the plasma protein binding rate of felodipine was carried out to provide method for monitoring the blood concentration felodipine. Drug containing dialysis solution0.2,0.4,0.8 mg.L-1 of low, middle and high concentration were prepared(n=3), experiments were end after 4,10,24,48 h to inspect the balance time of plasma protein, finally 24 h was set for the final balance time. The plasma protein binding rate of felodipine at low, middle and high concentrations were99.7%,99.5%,99.4% respectively, and the mean plasma protein binding rate of felodipine was99.43%.The binding rate of felodipine to human plasma protein was very high.To study pharmacokinetics and pharmacodynamics of felodipine in healthy volunteers. The regression of blood concentration in different time was made and the relative efficients of SBP、DBP and HR were 0.6146,0.9856,0.9077 respectively. The DBP and HR should be the key points of observation for its clinical use.