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 (C max ), time to peak plasma concentration ( T max ), area under the plasma concentration-time curve from 0 to the last time point ( AUC last ) or from time 0 to infinity ( AUC inf ), elimination half-life (t 1/2 ), clearance ( CL ), and volume of distribution ( Vd). The phentolamine T max occurred earlier following the intravenous administration of 1P iv (7 minutes than following its submucosal administration in treatment 1L1P (15 minutes ) or 4L2P (11 minutes). The phentolamine t1/2, CL, an d Vd values were similar for 1L1P, 1Piv, an d 4L2P. The T max for lidocaine occurred later and the C max for lidocaine was slightly higher when comparing the 4L2P treatment and the 4L treatment. The phentolamine-induced delay of the lidocaine T max likely represents phentolamine's
Local anesthetic solutions frequently contain vasoconstrictors to increase the depth and/or duration of anesthesia. Generally, the duration of soft-tissue anesthesia exceeds that of pulpal anesthesia. Negative consequences of soft-tissue anesthesia include accidental lip and tongue biting as well as difficulty in eating, drinking, speaking, and smiling. A double-blind, randomized, multicenter, Phase 2 study tested the hypothesis that local injection of the vasodilator phentolamine mesylate would shorten the duration of soft-tissue anesthesia following routine dental procedures. Participants (122) received one or two cartridges of local anesthetic/vasoconstrictor prior to dental treatment. Immediately after treatment, 1.8 mL of study drug (containing 0.4 mg phentolamine mesylate or placebo) was injected per cartridge of local anesthetic used. The phentolamine was well-tolerated and reduced the median duration of soft-tissue anesthesia in the lip from 155 to 70 min (p < 0.0001).
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