Chan H M, Duran S H, Walz P H, Ravis W R
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
J Vet Pharmacol Ther. 2009 Jun;32(3):235-40. doi: 10.1111/j.1365-2885.2008.01030.x.
Voriconazole is a new antifungal drug that has shown effectiveness in treating serious fungal infections and has the potential for being used in large animal veterinary medicine. The objective of this study was to determine the plasma concentrations and pharmacokinetic parameters of voriconazole after single-dose intravenous (i.v.) and oral administration to alpacas. Four alpacas were treated with single 4 mg/kg i.v. and oral administrations of voriconazole. Plasma voriconazole concentrations were measured by a high-performance liquid chromatography method. The terminal half-lives following i.v. and oral administration were 8.01 +/- 2.88 and 8.75 +/- 4.31 h, respectively; observed maximum plasma concentrations were 5.93 +/- 1.13 and 1.70 +/- 2.71 microg/mL, respectively; and areas under the plasma concentration vs. time curve were 38.5 +/- 11.1 and 9.48 +/- 6.98 mg.h/L, respectively. The apparent systemic oral availability was low with a value of 22.7 +/- 9.5%. The drug plasma concentrations remained above 0.1 microg/mL for at least 24 h after single i.v. dosing. The i.v. administration of 4 mg/kg/day voriconazole may be a safe and appropriate option for antifungal treatment of alpacas. Due to the low extent of absorption in alpacas, oral voriconazole doses of 20.4 to 33.9 mg/kg/day may be needed.
伏立康唑是一种新型抗真菌药物,已显示出在治疗严重真菌感染方面的有效性,并有用于大型动物兽医学的潜力。本研究的目的是确定伏立康唑在单剂量静脉注射(i.v.)和口服给药后在羊驼体内的血浆浓度和药代动力学参数。对四只羊驼进行了单次4mg/kg的伏立康唑静脉注射和口服给药。采用高效液相色谱法测定血浆伏立康唑浓度。静脉注射和口服给药后的终末半衰期分别为8.01±2.88小时和8.75±4.31小时;观察到的最大血浆浓度分别为5.93±1.13μg/mL和1.70±2.71μg/mL;血浆浓度-时间曲线下面积分别为38.5±11.1mg·h/L和9.48±6.98mg·h/L。表观口服全身可用性较低,为22.7±9.5%。单次静脉给药后,药物血浆浓度至少在24小时内保持在0.1μg/mL以上。静脉注射4mg/kg/天的伏立康唑可能是羊驼抗真菌治疗的安全且合适的选择。由于羊驼的吸收程度较低,可能需要口服20.4至33.9mg/kg/天的伏立康唑剂量。