EFFECT OF LIFE-GIVING LEAF EXTRACT (GYNURA PROCUMBENS) ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF NIFEDIPINE IN HIPERTENSIVE RATS

• Main Author: Nur Azalia Hasanuddin, Devy
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/80379
• Institution: Institut Teknologi Bandung

Hypertension is a leading cause of cardiovascular disease and premature death worldwide. Blood pressure in hypertensive patients can be controlled by taking antihypertensive drugs, for example nifedipine. Nifedipine is a dihydropyridine calcium channel blocker. The use of conventional drugs along with herbs has increased in hypertension therapy. One of the herbs that is often used in hypertension therapy is life-giving leaf extract (Gynura procumbens). This study aimed to evaluate the effect of life-giving leaf extract on the pharmacokinetic and pharmacodynamic interactions (lowering blood pressure) of nifedipine in a hypertensive rat model. The High-Performance Liquid Chromatography (HPLC) method for analyzing nifedipine in plasma was developed and validated including selectivity, carryover, linearity, accuracy, precision, recovery, and stability. Pharmacokinetic and pharmacodynamic study used an induced hypertension rat model L-Nitro-Arginine Methyl Ester (L-NAME) 40 mg/kg BW for 14 days, except that the group of healthy control rats (normal) were only given aquabidest. Pharmacokinetic study was carried out on two groups (n=3), namely the group given a single dose of nifedipine 1 mg/kg BW (NFD) and the group given nifedipine 1 mg/kg BW together with life-giving leaf extract 154 mg/kg BW (NFD+EDSN). Pharmacodynamic testing was carried out on five groups (n=3) including healthy controls (normal), hypertensive controls (L-NAME), nifedipine single dose 1 mg/kg BW (NFD), life-giving leaf extract 154 mg/kg BW (EDSN), and nifedipine 1 mg/kg BW together with life-giving leaf extract 154 mg/kg BW (NFD+EDSN). Rat blood pressure was measured using tail-cuff blood pressure system. The HPLC method for nifedipine analysis was proven to meet the requirements for selectivity and carryover, good linearity, has accuracy (% error) and precision (% coefficient of variation/CV) £15% except LLOQ £20%, recovery in the range of 97.39-107.89%, and stable in storage for 12 hours and 21 days at a temperature of -20° C. The pharmacokinetic profiles and parameters of nifedipine were calculated following a two-compartment model. Administration of life-giving leaf extract together with nifedipine did not show a significant difference in pharmacokinetic parameters in the group that was only given nifedipine. Systolic blood pressure (SBP1-4) and diastolic (DBP1-4) in the pharmacodynamic test showed a significant difference (p<0.05) between the NFD+EDSN group and the L-NAME group. The NFD and EDSN groups did not differ significantly (p>0.05) from the L-NAME group. Thus, administration of life-giving leaf extract together with nifedipine can increase the antihypertensive effect of nifedipine in L-NAME-induced hypertensive rats.