Department of Radiology, University of Michigan, Ann Arbor, MI 48105, USA.
Adamis Pharmaceuticals, 11682 El Camino Real, Suite # 300, San Diego, CA 92130, USA.
Molecules. 2020 Mar 17;25(6):1360. doi: 10.3390/molecules25061360.
Naloxone (NLX) is a mu receptor antagonist used to treat acute opioid overdoses. Currently approved doses of naloxone to treat opioid overdoses are 4 mg intranasal (IN) and 2 mg intramuscular (IM). However, higher mu receptor occupancy (RO) may be required to treat overdoses due to more potent synthetic opioids such as fentanyl and carfentanil that have entered the illicit drug market recently. To address this need, a higher dose of NLX has been investigated in a 5 mg IM formulation called ZIMHI but, while the effects of intravenous (IV) and IN administration of NLX on the opioid mu receptor occupancy (RO) have been studied, comparatively little is known about RO for IM administration of NLX. The goal of this study was to examine the effect of IM dosing of NLX on mu RO in rhesus macaques using [C]carfentanil positron emission tomography (PET) imaging. The lowest dose of NLX (0.06 mg/kg) approximated 51% RO. Higher doses of NLX (0.14 mg/kg, 0.28 mg/kg) resulted in higher mu RO of 70% and 75%, respectively. Plasma levels were 4.6 ng/mL, 16.8 ng/mL, and 43.4 ng/mL for the three IM doses, and a significant correlation between percent RO and plasma NLX level was observed (r = 0.80). These results suggest that higher doses of IM NLX result in higher mu RO and could be useful in combating overdoses resulting from potent synthetic opioids.
纳洛酮（NLX）是一种用于治疗急性阿片类药物过量的μ受体拮抗剂。目前批准的纳洛酮治疗阿片类药物过量的剂量为 4 毫克鼻内（IN）和 2 毫克肌肉内（IM）。然而，由于最近进入非法毒品市场的芬太尼和卡芬太尼等更有效的合成阿片类药物，可能需要更高的μ受体占有率（RO）来治疗过量。为了解决这一需求，一种更高剂量的 NLX 已在 5 毫克 IM 制剂 ZIMHI 中进行了研究，但尽管已经研究了 NLX 的静脉内（IV）和 IN 给药对阿片类μ受体占有率（RO）的影响，但对于 IM 给药的 NLX 的 RO 知之甚少。本研究的目的是使用 [C]卡芬太尼正电子发射断层扫描（PET）成像研究 IM 给予 NLX 对猕猴μ RO 的影响。最低剂量的 NLX（0.06mg/kg）接近 51%的 RO。较高剂量的 NLX（0.14mg/kg，0.28mg/kg）分别导致更高的 μ RO 达到 70%和 75%。三种 IM 剂量的血浆水平分别为 4.6ng/mL、16.8ng/mL 和 43.4ng/mL，并且观察到 RO 百分比与血浆 NLX 水平之间存在显著相关性（r=0.80）。这些结果表明，IM NLX 的较高剂量导致更高的 μ RO，并且可能有助于对抗由强效合成阿片类药物引起的过量。
