Drug-Drug Interaction Between Amlodipine And Clarithromycin In Hypertension Rabbits

Abstract

This study is the first to examine the possibility of pharmacokinetic interaction in blood circulation using amlodipine and clarithromycin as representatives in hypertension rabbits and identify changes. The current study design required rabbits (n=6) for Pharmacokinetics. In group A, rabbits without treatment were used as control. In group B, were administration of a single dose of amlodipine (0.21mg/kg.BW) for 24 hours. Group C, were administered with a single dose of amlodipine (0.21mg/kg/BW.) and clarithromycin (22 mg/kg/BW.) each 6 hr. for 24 hour. The blood samples were collected from (B and C) groups at time intervals of zero, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144 hours and the drug concentrations were estimated using a spectrophotometer and estimated blood pressure using blood pressure cuff with Doppler ultrasound transducer. An increase in C max and AUC in group C (3.52 μg/ml and 130 μg/ml*h) respectively, indicates the improved bioavailability of amlodipine in the presence of clarithromycin compared with group B (2.03 μg/ml and 96.10 μg/ml*h) respectively. Furthermore, reduction in (CL) with an elevation of (Vd) in the presence of clarithromycin (54.94 L/kg/hr. and 4994 L/kg) in group C respectively, compared with group B (74.31 L/kg/hr and 3715 L/kg) respectively. We studied the influence of clarithromycin on the pharmacodynamics of amlodipine in hypertension rabbits. Interaction of amlodipine with multiple doses of clarithromycin produced a high reduction in blood pressure at 9 after administration and the blood pressure continues redaction. In conclusion, the combination of amlodipine with clarithromycin led to the enhancement of the bioavailability of amlodipine by inhibiting the CYP3A4 enzyme leading to producing a hypotension effect with peak plasma concentration effect in hypertension rabbits.