| Transdermal administration can exert therapeutical effect after drug permeated skin. Compared with oral administration and injection administration, transdermal administration is more convenient to use, is smaller stress reaction, and is lower toxic side effects, can avoid the hepatic first-pass metabolism, and can provide steady-state plasma level of drug and long-term therapy, and so on. The transdermal rate of drugs is the key factor to exerting therapy effect. Using transdermal enhancer to increase penetration rate is the most common technique. In this paper, several transdermal enhancers are used to develop transdermal agent of eprinomectin. The pest control effect of eprinomectin transdermal agent and the elimination rule of eprinomectin in yak plasma and milk following topical administration at a dose of0-5mg/kg were discussed. According to the orthogonal arrays related L25(56),25transdermal agent samples containing0.10g eprinomectin were developed with Azone, propylene glycol, oleic acid and dimethyl sulfoxide. Transdermal test was studied with YB-P6smart transdermal instrument and rat’s skin in vitro. The ransdermal rat of25samples were detected and analysised through high-performance liquid Chromatography. The optimal prescription Azone2%, and6%oleic acid,8%of propylene glycol,40%dimethyl sulfoxide was screened out according to the tenth hour’cumulative permeation concentration.45healthy yaks were divided into three groups randomly (n=15), control group (no drug), injection group (injected a commercial injection eprinomectin of0.2mg/kg), transdermal administered group (topically administered the transdermal agent of eprinomectin of0.5mg/kg). The pest control effect was detected with precipitation for seven weeks after treatment. The highest decrease rate of eggs occurred third week,92.72%and97.09%for transdermal group and injection group, respectively. During the entire experiment, there was no redness, allergies, dehair and peel at the site of smearing; there were no signs of intoxication for yaks; the yaks’production performance was no drop; the transdermal agent did not induced any other skin diseases. The transdermal agent of eprinomectin is efficient and safe for yak, and the recommended dose is0.5mg/kg.6clinically healthy adult yaks and6clinically healthy lactating yaks were divided into transdermal group (topically administered the transdermal agent of eprinomectin of0.5mg/kg) and injection group (injected a commercial injection eprinomectin of0.2mg/kg) randomly (n=3). Blood/milk (5ml) samples were collected from each yak’s jugular vein at0(prior to treatment), after0.5,1,1.5,2,3,4,5,6,8,10,12,15,21,25,31,40days and4th,8th hour blood for injection group post-treatment. Eprinomectin was extracted from the plasma and milk samples with acetonitrile and was further cleaned up using a ProElut PLS solid phase extraction column, before analysed with LC-MS system. The pharmacokinetic parameters of eprinomectin in yak plasma andmilk were determined suing a two-compartment method. AUC values were146.52±76.34and41.63±20.37ng day/mL in yak plasma and milk; MRT of eprinomectin in plasma and milk of the yak were7.20±1.44and9.10±5.87days. The concentrations of eprinomectin in plasma reached peak values (Cmax) of15.62±3.71ng/ml at3.04±1.22days. In milk, the Cmax values3.75±2.15ng·ml-1were obtained at2.99±0.88day. In plasma, the absorption half-life t1/2ka=1.34±0.89days, distribution half-life t1/2kd=2.85±1.74days, elimination half-life t1/2ke=3.82±2.01days. In mink, t1/2ka=1.08±0.43days, t1/2kd=3.26±1.68, t1/2ke=5.72±3.04.The absorption half-life, the time to peak, elimination half-life, the average residual time of transdermal agent of eprinomectin is longer than injection, and the Cmax is lower than injection. The transdermal agent of eprinomectin is more safety and more efficient than injection... |
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