Alavi F K, Alavi K, McCann J P, Sangiah S, Clarke C R
Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078-0353.
Can J Physiol Pharmacol. 1994 May;72(5):471-5. doi: 10.1139/y94-068.
Naloxone is an opioid antagonist used frequently in studies of appetite regulation in lean and obese animals and humans. Body condition may affect plasma and tissue distribution of injected naloxone and thus confound interpretation of responses to naloxone in lean compared with obese subjects. The objective of this experiment was to determine the effect of dietary obesity per se on the pharmacokinetic behavior of iv-injected naloxone (3 mg/kg) in lean (46 kg body weight) and dietary obese (77 kg body weight) sheep that were maintained at equilibrium weight. To this end, an HPLC procedure combined with electrochemical detection was developed for measuring naloxone in sheep plasma. Naloxone disappearance from plasma followed an apparent first-order process, the kinetics of which were described best using a two-compartment open model. Components of the biexponential equations describing the plasma concentration (C)-time (t) curves for naloxone disappearance in lean (Ct = 1814e(-0.190t) + 413e(-0.017t)) and obese (Ct = 2282e(-0.282t) + 573e(-0.018t)) sheep were similar (p > 0.05). Mean (+/- SE) elimination half-lives for naloxone in lean (42.7 +/- 4.6 min) and obese (44.3 +/- 10.2 min) sheep were similar (p > 0.05). Volume of distribution of naloxone (Vd) was extensive but also similar (p > 0.05) in lean (5.6 +/- 0.9 L/kg) and obese (4.1 +/- 0.6 L/kg) sheep. Naloxone was distributed extensively throughout the body fluids and trapped or stored in significant amount in extravascular tissues because the naloxone Vd greatly exceeded 100% of body weight in both lean (557 +/- 86 mL/100 g) and obese (413 +/- 58 mL/100 g) sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
纳洛酮是一种阿片类拮抗剂，常用于对瘦型和肥胖型动物及人类的食欲调节研究。身体状况可能会影响注射用纳洛酮的血浆和组织分布，从而使与肥胖受试者相比，瘦型受试者对纳洛酮反应的解释变得复杂。本实验的目的是确定单纯饮食性肥胖对静脉注射纳洛酮（3mg/kg）在维持体重平衡的瘦型（体重46kg）和饮食性肥胖型（体重77kg）绵羊体内药代动力学行为的影响。为此，开发了一种结合电化学检测的高效液相色谱法来测定绵羊血浆中的纳洛酮。纳洛酮从血浆中的消失遵循表观一级过程，用二室开放模型能最好地描述其动力学。描述瘦型（Ct = 1814e(-0.190t) + 413e(-0.017t)）和肥胖型（Ct = 2282e(-0.282t) + 573e(-0.018t)）绵羊体内纳洛酮消失的血浆浓度（C）-时间（t）曲线的双指数方程的组成部分相似（p > 0.05）。纳洛酮在瘦型（42.7 +/- 4.6分钟）和肥胖型（44.3 +/- 10.2分钟）绵羊体内的平均（+/- SE）消除半衰期相似（p > 0.05）。纳洛酮的分布容积（Vd）很大，但在瘦型（5.6 +/- 0.9 L/kg）和肥胖型（4.1 +/- 0.6 L/kg）绵羊体内也相似（p > 0.05）。纳洛酮广泛分布于全身体液中，并大量滞留或储存在血管外组织中，因为在瘦型（557 +/- 86 mL/100 g）和肥胖型（413 +/- 58 mL/100 g）绵羊体内，纳洛酮的Vd都大大超过了体重的100%。（摘要截于250字）
