Toutain P L, Brandon R A, Alvinerie M, Garcia-Villar R, Ruckebusch Y
J Vet Pharmacol Ther. 1982 Mar;5(1):33-43. doi: 10.1111/j.1365-2885.1982.tb00496.x.
The pharmacokinetics of Dexamethasone (DXM) was studied in four cows all of which received DXM alcohol and DXM 21 isonicotinate (as a solution) by the intravenous and intramuscular routes. Concentrations of DXM and cortisol were determined using high performance liquid chromatography. An additional study was made in a second group of four cows which received intramuscular DXM 21 isonicotinate suspension for the assessment of DXM suppression of adrenal gland function. This was determined by measurements of base-line and ACTH-stimulated cortisol concentrations, before and following DXM administration. Following intravenous administration, the disposition kinetics of both formulations were described by a two-compartment open model. The half-times of elimination were similar; 335 and 291 min, respectively, for DXM alcohol and DXM 21 isonicotinate. All other pharmacokinetic parameters were not statistically different indicating that DXM was almost totally available (from DXM 21 isonicotinate). Following intramuscular administration, no significant difference in parameters was observed between the two formulations. Peak plasma concentrations were reached at 3 to 4 h post injection and bioavailability was approximately 70%. DXM was not detected in the plasma after the intramuscular administration of the suspension. The mean control plasma cortisol concentration was 8.8 +/- 3.03 ng/ml. Following intravenous and intramuscular administrations of DXM alcohol and DXM 21 isonicotinate (solution), cortisol concentrations initially increased. However, at 120 min (intravenous) and 2-4 h (intramuscular), concentrations were negligible; 24-72 h and 48-96 h, respectively elapsed before concentrations returned control values. Following DXM 21 isonicotinate (suspension) there was no initial increase and concentrations had not returned to normal in all four cows until 52 days post administration. Similarly, ACTH-stimulated plasma cortisol concentrations decreased progressively and significantly post administration. At 52 days, response to ACTH was normal in all animals.
在地塞米松（DXM）的药代动力学研究中，选取了四头奶牛，通过静脉注射和肌肉注射途径，分别给予它们地塞米松醇和地塞米松21异烟酸盐（溶液）。采用高效液相色谱法测定DXM和皮质醇的浓度。在另一组四头奶牛中进行了额外研究，这些奶牛接受肌肉注射地塞米松21异烟酸盐混悬液，以评估DXM对肾上腺功能的抑制作用。这通过在给予DXM之前和之后测量基线及促肾上腺皮质激素（ACTH）刺激后的皮质醇浓度来确定。静脉注射后，两种制剂的处置动力学均可用二室开放模型描述。消除半衰期相似；地塞米松醇和地塞米松21异烟酸盐的消除半衰期分别为335分钟和291分钟。所有其他药代动力学参数无统计学差异，表明DXM几乎完全可从地塞米松21异烟酸盐中获得。肌肉注射后，两种制剂之间未观察到参数有显著差异。注射后3至4小时达到血浆峰值浓度，生物利用度约为70%。肌肉注射混悬液后，血浆中未检测到DXM。对照血浆皮质醇平均浓度为8.8±3.03纳克/毫升。静脉注射和肌肉注射地塞米松醇及地塞米松21异烟酸盐（溶液）后，皮质醇浓度最初升高。然而，在静脉注射120分钟和肌肉注射2至4小时时，浓度可忽略不计；分别在24至72小时和48至96小时后，浓度才恢复到对照值。给予地塞米松21异烟酸盐（混悬液）后，浓度没有初始升高，直到给药后52天，所有四头奶牛的浓度才恢复正常。同样，给药后ACTH刺激的血浆皮质醇浓度逐渐且显著降低。在52天时，所有动物对ACTH的反应均正常。
