The Effect Of Amlodipine Besylate Through Percutaneous Penetration On The Survival Of Random Ischemic Skin Flaps

ObjectiveTo investigate the accumulate amounts of different concentrations of amlodipine besylate gels through excised rat and mouse skin and select out relatively lower concentration of amlodipine besylate gel which could achieve its minimum effective concentration, then observe its effect on the survival of ischemic skin flaps and simultaneously assay the quantities of amlodipine besylate within flaps to find out the relationship between two of them.MethodModified Franz diffusion cells were used in our in vitro experiment, and the accumulate amounts of amlodipine besylate through excised rat and mouse skin were determined by UV-spectrometer at appropriate intervals after application to select out ideal penetration enhancers and relatively lower concentration of amlodipine gel which could achieve its minimum effective concentration. An ischemic skin flap measuring 10mm×80mm was established on the back of each rat with pedicle at the tail side, two gramma of pure gel without amlodipine besylate, 0.5% and 1.5% amlodipine besylate gels were immediately applied on the skin flaps after the flap surgery ended. The respective once daily application was continued for 7 days after operation. The viable areas of skin flaps were assessed on the seventh postoperative day by using the squared paper method. At 2 and 6 hours after application of amlodipine besylate gel, lg flap, tissue (axial portion) was excised, and then the quantities of amlodipine besylate were determined by UV-spectrophotometer after the skin were homogenized and extracted.Result1. The accumulative amounts of 0.5% and 1.5% amlodipine besylate gels were lower than 1.5%, 2.0% and 2.5% amlodipine besylate gels(P<0.05), and no statistically difference showed between 0.5% and 1.0 % amlodipine besylate gels, it is also the same when 1.5%, 2.0% and 2.5% amlodipine besylate gels compared with each other respectively. Meanwhile the increasing of accumulative amounts of each gel was in a concentration-and time-dependent manner(P<0.05).2. The survival areas related to the control group were significantly improved from 192.9±56.8mm~2 to 391.4±65.4mm~2 by 0.5% amlodipine besylate gel (P<0.05). Though 1.5% amlodipine besylate gel also showed same tendency (265.7±88.3mm~2), no significant difference was seen between group B and C (P=0.217).3. The quantities of amlodipine besylate within flaps were higher in group A than group B(P<0.05).Conclusion1. Accumulative quantities of amlodipine besylate through excised rat and mouse skin were increased in a concentration- and time-dependent manner.2. 0.5% amlodipine besylate gel had the best effect on the survival of ischemic random skin flaps.