Jones R D, Mizinga K M, Thompson F N, Stuedemann J A, Bowen J M
Department of Veterinary Physiology and Pharmacology, University of Georgia, Athens 30602.
J Vet Pharmacol Ther. 1994 Apr;17(2):141-7. doi: 10.1111/j.1365-2885.1994.tb00224.x.
The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (+/- SD) oral and abomasal bioavailabilities were 51.3 +/- 30.7% and 76.2 +/- 15.5%, respectively. The mean value for clearance (Cl) was 20.1 +/- 5.9 ml/min and the volume of distribution (Vd) was 0.51 +/- 0.19 l/kg. Additional pharmacokinetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t 1/2 alpha harmonic mean of 24.2 min and a range of 11.2-72.4 min, a t 1/2 beta harmonic mean of 53.1 min and a range of 31.1-134.1 min, a Cl of 42.2 +/- 8.7 ml/min, and a Vd of 2.1 +/- 0.8 l/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment-by-subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady-state metoclopramide concentration (MCPss) of 8.8 +/- 2.6 ng/ml was associated with a three-fold elevation of prolactin to a mean value of 12.1 +/- 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations (PRLss) did not rise significantly above 23.3 +/- 6.9 ng/ml, even when MCPss reached a concentration of 518.5 +/- 151.2 ng/ml. The short half-life, moderate Vd, low minimum pharmacologically effective concentration, and rapid Cl found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.
采用拉丁方设计，对三头阉牛分别经口服、皱胃（插管）和静脉途径给予8mg/kg甲氧氯普胺后，研究了其生物利用度。口服和皱胃给药的平均（±标准差）生物利用度分别为51.3±30.7%和76.2±15.5%。清除率（Cl）的平均值为20.1±5.9ml/min，分布容积（Vd）为0.51±0.19l/kg。对七头奶牛静脉注射甲氧氯普胺后，测定了其其他药代动力学参数。在六头奶牛中发现了一个主要的二室分布模型，t1/2α谐波平均值为24.2分钟，范围为11.2 - 72.4分钟；t1/2β谐波平均值为53.1分钟，范围为31.1 - 134.1分钟；Cl为42.2±8.7ml/min，Vd为2.1±0.8l/kg。为了更好地确定甲氧氯普胺浓度与催乳素释放之间的关系，进行了一项受试者治疗输注研究，使用了四种不同的负荷剂量随后进行持续输注。在六头一岁阉牛中，稳态甲氧氯普胺浓度（MCPss）为8.8±2.6ng/ml时，催乳素升高了三倍，平均值为12.1±3.1ng/ml。即使MCPss达到518.5±151.2ng/ml的浓度，稳态血清催乳素浓度（PRLss）也未显著升高至23.3±6.9ng/ml以上。本研究中在牛体内发现的甲氧氯普胺半衰期短、分布容积适中、最低药理有效浓度低以及清除率快，表明持续释放装置可能在该药物预防和治疗牛茅草中毒的应用中具有潜在用途。
