Abstract：
OBJECTIVE: To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age.
METHODS: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old).
METHODS: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant.
RESULTS: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups.
CONCLUSIONS: The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.
METHODS: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old).
METHODS: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant.
RESULTS: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups.
CONCLUSIONS: The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.
摘要：
目的：通过表征PBZ及其活性代谢物的药代动力学特征，评估衰老对老年马（≥25岁）与青壮年（4至10岁）的保泰松（PBZ）分布的影响，氧苯丁酮（OPBZ），在2.2mg/kg剂量后，IV.我们假设PBZ的处置会受到年龄的影响。
方法：16匹健康马（8名4至10岁的年轻成年人和8名≥25岁的老年马）。
方法：对马匹进行单次2.2mg/kgPBZ剂量，IV.在指定时间点收集血浆样品并在-80°C下冷冻直至使用液相色谱-串联质谱法测定。使用PhoenixWinNonlin进行药代动力学分析，8.0版（Certara）。使用独立样本t检验比较年龄组之间的临床和药代动力学数据，P<0.05被认为是显著的。
结果：基线特征在组间没有差异，除了年龄,体重,和血浆总固体。PBZ的血浆浓度最好通过两室模型来描述。两个年龄组在5小时时达到OPBZ的最大血浆浓度，两组的代谢物与母体药物的曲线下面积比约为20%.PBZ或其代谢物的药代动力学参数，OPBZ,年龄组之间差异显著。
结论：该假设被拒绝，因为与老年马相比，年轻成年马的PBZ倾向没有显着差异。我们的数据不支持在临床健康的老年马中需要调整PBZ的剂量。
方法：16匹健康马（8名4至10岁的年轻成年人和8名≥25岁的老年马）。
方法：对马匹进行单次2.2mg/kgPBZ剂量，IV.在指定时间点收集血浆样品并在-80°C下冷冻直至使用液相色谱-串联质谱法测定。使用PhoenixWinNonlin进行药代动力学分析，8.0版（Certara）。使用独立样本t检验比较年龄组之间的临床和药代动力学数据，P<0.05被认为是显著的。
结果：基线特征在组间没有差异，除了年龄,体重,和血浆总固体。PBZ的血浆浓度最好通过两室模型来描述。两个年龄组在5小时时达到OPBZ的最大血浆浓度，两组的代谢物与母体药物的曲线下面积比约为20%.PBZ或其代谢物的药代动力学参数，OPBZ,年龄组之间差异显著。
结论：该假设被拒绝，因为与老年马相比，年轻成年马的PBZ倾向没有显着差异。我们的数据不支持在临床健康的老年马中需要调整PBZ的剂量。
