Moore Paul A, Hersh Elliot V, Papas Athena S, Goodson J Max, Yagiela John A, Rutherford Bruce, Rogy Seigried, Navalta Laura
Department of Anesthesiology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Anesth Prog. 2008 Summer;55(2):40-8. doi: 10.2344/0003-3006(2008)55[40:POLWEF]2.0.CO;2.
Phentolamine mesylate accelerates recovery from oral soft tissue anesthesia in patients who have received local anesthetic injections containing a vasoconstrictor. The proposed mechanism is that phentolamine, an alpha-adrenergic antagonist, blocks the vasoconstriction associated with the epinephrine used in dental anesthetic formulations, thus enhancing the systemic absorption of the local anesthetic from the injection site. Assessments of the pharmacokinetics of lidocaine and phentolamine, and the impact of phentolamine on the pharmacokinetics of lidocaine with epinephrine were performed to characterize this potentially valuable strategy. The blood levels of phentolamine were determined following its administration intraorally and intravenously. Additionally, the effects of phentolamine mesylate on the pharmacokinetics of intraoral injections of lidocaine with epinephrine were evaluated. Sixteen subjects were enrolled in this phase 1 trial, each receiving 4 drug treatments: 1 cartridge lidocaine/epinephrine followed after 30 minutes by 1 cartridge phentolamine (1L1P), 1 cartridge phentolamine administered intravenously (1Piv), 4 cartridges lidocaine/epinephrine followed after 30 minutes by 2 cartridges phentolamine (4L2P), and 4 cartridges lidocaine/epinephrine followed by no phentolamine (4L). Pharmacokinetic parameters estimated for phentolamine, lidocaine, and epinephrine included peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve from 0 to the last time point (AUClast) or from time 0 to infinity (AUCinf), elimination half-life (t1/2), clearance (CL), and volume of distribution (Vd). The phentolamine Tmax occurred earlier following the intravenous administration of 1Piv (7 minutes than following its submucosal administration in treatment 1L1P (15 minutes) or 4L2P (11 minutes). The phentolamine t1/2, CL, and Vd values were similar for 1L1P, 1Piv, and 4L2P. The Tmax for lidocaine occurred later and the Cmax for lidocaine was slightly higher when comparing the 4L2P treatment and the 4L treatment. The phentolamine-induced delay of the lidocaine Tmax likely represents phentolamine's ability to accelerate the systemic absorption of lidocaine from oral tissues into the systemic circulation.
甲磺酸酚妥拉明可加速接受含有血管收缩剂的局部麻醉注射患者口腔软组织麻醉的恢复。其推测机制是，酚妥拉明作为一种α-肾上腺素能拮抗剂，可阻断与牙科麻醉制剂中使用的肾上腺素相关的血管收缩，从而增强局部麻醉剂从注射部位的全身吸收。为了表征这一潜在的有价值策略，对利多卡因和酚妥拉明的药代动力学以及酚妥拉明对利多卡因与肾上腺素联合用药药代动力学的影响进行了评估。在口服和静脉给药后测定了酚妥拉明的血药浓度。此外，还评估了甲磺酸酚妥拉明对口腔注射利多卡因与肾上腺素联合用药药代动力学的影响。16名受试者参加了这项1期试验，每人接受4种药物治疗：1支利多卡因/肾上腺素，30分钟后注射1支酚妥拉明（1L1P）；静脉注射1支酚妥拉明（1Piv）；4支利多卡因/肾上腺素，30分钟后注射2支酚妥拉明（4L2P）；4支利多卡因/肾上腺素，不注射酚妥拉明（4L）。酚妥拉明、利多卡因和肾上腺素的药代动力学参数包括血浆峰浓度（Cmax）、达峰时间（Tmax）、从0至最后一个时间点的血浆浓度-时间曲线下面积（AUClast）或从时间0至无穷大的血浆浓度-时间曲线下面积（AUCinf）、消除半衰期（t1/2）、清除率（CL）和分布容积（Vd）。静脉注射1Piv后酚妥拉明的Tmax出现得更早（7分钟），而在治疗1L1P（黏膜下给药，15分钟）或4L2P（黏膜下给药，11分钟）中则较晚。1L1P、1Piv和4L2P的酚妥拉明t1/2、CL和Vd值相似。与4L治疗相比，4L2P治疗中利多卡因的Tmax出现得更晚，利多卡因的Cmax略高。酚妥拉明引起的利多卡因Tmax延迟可能代表酚妥拉明加速利多卡因从口腔组织全身吸收进入体循环的能力。
