[Percutaneous penetration ability of dexamethasone-amlodipine besylate compound gel and its effect on survival of ischemic random skin flap].
OBJECTIVE
Dexamethasone (DXM) can regulate the balance of neutrophil and cytokine and enhance the ischemia-reperfusion tolerance of the skin flap; amlodipine besylate (AB) can selectively expand the peripheral blood vessels and relieve the vascular smooth muscle spasm. To investigate the percutaneous penetration ability of DXM/AB compound gel and evaluate its effect on survival of ischemic skin flap.


METHODS
Sodium carboxymethylcellulose was used to make blank gel, which was mixed in DXM, AB, azone (AZ), and propylene glycol (PG) respectively to make the compound gel containing 0.3%DXM/0.5%AB only (group D), the compound gel containing 3%AZ/2%PG, 3%AZ, and 2%PG (groups A, B, and C), the 0.3%DXM gel containing 3%AZ/2%PG (group E), the 0.5%AB gel containing 3%AZ/2%PG (group F). The accumulative penetration of DXM and AB in compound gel, 0.3%DXM gel, 0.5%AB gel through excised rat skin and its penetration within flap tissue were investigated by ultraviolet spectrophotometry. Fifty SD rats were selected to make 100 mm x 10 mm random flap at the back, and were randomly divided into 5 groups according to different gels which were used to treat flaps (n = 10): compound gel group (group A1), 0.3%DXM gel group (group B1), 0.5%AB gel group (group C1), blank gel group (group D1), and peritoneal injection of DXM (5 mg/kg) and AB (2 mg/kg) (group E1). The survival area of ischemic random skin flap was measured on the 7th day by planimetry. Twenty-four SD rats were selected to make 100 mm x 10 mm random flap at the back, and were randomly divided into 2 groups (n = 12). The accumulative penetration of DXM and AB within skin flap were also detected at 2 and 6 hours after application of 2 g of compound gel containing 3%AZ/2%PG (group A2) and peritoneal injection AB (2 mg/kg) / DXM (5 mg/kg) (group B2).


RESULTS
The accumulative penetration of DXM and AB in compound gel were increased in time-dependent manner (P < 0.05), and it was the highest in group A, and was significantly higher than that in group B and group C (P < 0.01), but there was no significant difference when compared with group E or group F (P > 0.05). The accumulative penetration of DXM and AB in groups A, B, and C were significant higher than that in group D (P < 0.05). After 7 days, the survival area of flaps in groups A1, B1, C1, D1, and E1 were (695.0 +/- 4.6), (439.3 +/- 7.1), (477.5 +/- 14.5), (215.2 +/- 3.8), and (569.4 +/- 9.7) mm2, respectively; group A1 was significantly higher than other groups (P < 0.05). After 2 and 6 hours, the quantities of DXM and AB in skin flap of group A2 were significantly higher than that of group B2 (P < 0.05).


CONCLUSIONS
In 0.3%DXM/0.5%AB compound gel, DXM and AB might penetrate into skin tissue, which could significantly increase the survival area of ischemic skin flap.
Wang
Xiaolong
X
Department of Plastic Surgery, Second Hospital of Lanzhou University, Lanzhou Gansu 730030, PR China.
Zhang
Xuanfen
X
Qin
Yonghong
Y
Zhong
Lin
L
Liu
Kai
K
Zhang
Jin
J
D017311:Amlodipine / Q000493:pharmacokinetics*; D000818:Animals; D003907:Dexamethasone / Q000493:pharmacokinetics*; D005782:Gels; D006085:Graft Survival / Q000187:drug effects*; D007511:Ischemia; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D012867:Skin / Q000098:blood supply; D016038:Skin Transplantation; D013524:Surgical Flaps
D005782:Gels; D017311:Amlodipine; D003907:Dexamethasone