单次灌胃、静脉注射和肌内注射后多西环素在麻鸭体内的药动学

Pharmacokinetics of doxycycline after a single oral,intravenous or intramuscular dose in sheldrake ducks

对麻鸭单次静脉注射、肌内注射和灌胃多西环素后进行药动学研究,给药剂量均为20 mg/kg。麻鸭给药后定点采血,分离血浆,然后以高效液相色谱法测定血浆中的药物浓度,并利用房室分析法计算3种不同给药途径下多西环素的药动学参数。结果显示:静脉注射后,多西环素分布广泛,其表观分布容积(V_d)为(768.50±119.61)m L·kg^(-1),且消除缓慢,消除半衰期(t_(1/2β))为(16.62±0.84)h;而灌胃和肌内注射后,多西环素均迅速吸收,峰浓度(C_(max))分别为(11.32±3.46),(19.70±2.79)mg·L^(-1),达峰时间(t_(max))分别为(2.51±0.23),(1.56±0.09)h,绝对生物利用度则分别为39.44%,77.67%。本研究结果证实多西环素在麻鸭体内具有优异的药动学特征,其吸收迅速、分布广泛、消除缓慢,但同时灌胃后其生物利用度较低。因此推荐多西环素在麻鸭感染性疾病治疗中的给药方案为灌胃或肌内注服给药,剂量均为20 mg·kg^(-1)·d^(-1),连用3 d。

The pharmacokinetics of doxycycline in sheldrake ducks were investigated after a single intravenous （IV） ,intramuscular （IM） and oral （PO） dose of 20 mg/kg body weight. The concen- trations of doxycycline in plasma samples were assayed using a high performance liquid chroma-tography （HPLC） method and pharmacokinetic parameters were calculated by compartmental a- nalysis. After IV administration, doxycycline was extensively distributed with a distribution volume （Vd） of （768. 50±119. 61） mL·kg^-1 and slowly eliminated with an elimination half-life （t1/213） of （16. 62±0. 84） h. Following PO and IM administration, doxycycline was rapidly ab-sorbed. And the peak concentration （Cmax） was （11. 32±3. 46） mg·kg^-1 at （2. 51±0. 23） h and （19.70±2.79） mg·kg^-1 at （1.56±0.09） h,respectively. The absolute bioavailability （F） of dox- ycycline after PO and IM administration was 39.44% and 77.67%,respectively. The plasma pro file of doxycycline exhibited favourable pharmacokinetics characteristics in sheldrake ducks, such as wide distribution, rapid absorption and slow elimination, though oral bioavailability was low. A multiple-dosing regimen of doxycycline （an oral or intramuscular dose of 20 mg·kg^-1·d^-1 for 3 consecutive days） was recommended to treat the infections in sheldrake ducks.