Systemic Pharmacokinetics of Topical Intranasal Cocaine in Healthy Subjects

Background Topical cocaine is currently available for local anesthesia of the upper airway mucous membranes. Objective The objective of this study was to define the safety and efficacy of topical intranasal cocaine for a subsequent phase II clinical trial. Methods This study was a single-dose, single-center, and open-label study of the plasma and urinary pharmacokinetics (PK) of 4% topical cocaine and its major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), in 30 healthy subjects. Subjects received the topical solution on cotton pledgets containing 4 mL of 4% topical cocaine applied for 20 minutes, which was equivalent to 160 mg of cocaine hydrochloride. Results A total of 30 subjects (14 males and 16 females) were enrolled, treated, and provided PK data for analysis. Mean plasma concentrations of cocaine rose rapidly during the intranasal exposure period, with peak levels (Cmax, 37.0 ± 17.3 ng/mL) observed at the time of pledget removal (Tmax, 0.43 ± 0.34 h). Mean plasma concentrations then fell rapidly and monoexponentially for the remainder of the study, with a mean half-life (t1/2) of 1.04 ± 0.35 hours. Following a 20-minute topical intranasal exposure to a 160 mg dose of cocaine 4% solution, the mean 0 to 12 hours recoveries of cocaine, BE, and EME were 117 ± 67 μg, 816 ± 440 μg, and 275 ± 113 μg, respectively. Plotting urinary recovery by collection interval showed that urinary excretion of cocaine closely followed the time course of plasma cocaine. Conclusions Cocaine was rapidly but incompletely absorbed and then rapidly eliminated. Only 4% of the administered cocaine dose appeared to be absorbed in this study. Cocaine appeared in the urine with a time course similar to that in plasma.