Wilcke J R, Crisman M V, Scarratt W K, Sams R A
Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061, USA.
Am J Vet Res. 1998 Mar;59(3):290-2.
To determine pharmacokinetic variables that describe disposition of ketoprofen after its i.v. administration to foals < 24 hours old.
6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.
Ketoprofen was administered i.v. to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis.
Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours.
Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity.
确定描述小于24小时龄马驹静脉注射酮洛芬后处置情况的药代动力学变量。
6匹健康马驹(1匹雄性和5匹雌性);给药时平均年龄为12.5(范围为8.5至17)小时。
以2.2mg/kg体重的剂量给马驹静脉注射酮洛芬。采用高效液相色谱法分析血浆样本中的酮洛芬浓度。根据标准药代动力学技术分析浓度-时间曲线。在48小时内的特定时间通过颈静脉穿刺从马驹采集血样。样本离心后,血浆在-70℃冷冻直至分析。进行一室、二室和三室分析。使用赤池信息准则分析确定最合适的模型。
使用二室开放模型能最好地描述血浆浓度-时间曲线。清除率(按体重标准化)显著低于成年马。分布容积(按体重标准化)大于成年马。小于24小时龄健康马驹的平均(调和)血浆半衰期为4.3小时。
尽管必须根据具体情况考虑其他因素,如脱水或败血症,但小于24小时龄马驹的酮洛芬给药剂量应与成年马不同。在相似临床情况下,马驹的剂量应增加多达1.5倍以产生相当的治疗浓度;根据临床反应延长给药间隔以避免药物毒性是必要的。