Journal of clinical pharmacology
February 1, 2015
Paul Glue, Michelle Lockhart, Fred Lam et al.
61 citations
Noribogaine, the active metabolite of ibogaine, may help suppress withdrawal symptoms in opioid-dependent people. In a Phase I ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, oral doses of 3, 10, 30, or 60 mg were given. Noribogaine was rapidly absorbed, reaching peak concentrations 2-3 hours after dosing, and showed dose-linear increases in exposure between 3 and 60 mg. The drug was slowly eliminated, with mean half-lives of 28-49 hours and a high volume of distribution (mean 1417-3086 L). No safety or tolerability issues were identified, and no mu-opioid agonist effects were observed in pupillometry or cold-pressor testing. Single oral doses of 3-60 mg were safe and well tolerated.
Journal of clinical pharmacology
February 17, 2020
P. Glue, N. Medlicott, P. Surman et al.
44 citations
Oral controlled-release ketamine tablets improve safety and tolerability compared with injected ketamine by reducing peak drug exposures. In a randomized, placebo-controlled ascending-dose study of 24 healthy volunteers, doses of 60, 120, or 240 mg or placebo were given. Drug release occurred over about 10 hours, with most drug present as norketamine (approximately 90%). Elimination half-life was prolonged (7–9 hours) versus published data from immediate-release oral forms. No changes in blood pressure or heart rate occurred after any dose. Mild dissociation was reported only after 240 mg, with mean ratings of 1–2 out of 76. No clinically significant ECG or lab changes were observed. Reducing and delaying peak ketamine concentration improves tolerability for patients with depression or anxiety.
Journal of clinical pharmacology
June 1, 2015
Paul Glue, Helen Winter, Kira Garbe et al.
39 citations
Conversion of ibogaine to its active metabolite noribogaine is primarily mediated by the CYP2D6 enzyme. In a study of 21 healthy subjects given a single 20 mg oral dose of ibogaine after 6 days of pretreatment with either placebo or the CYP2D6 inhibitor paroxetine, those pretreated with paroxetine showed rapid absorption of ibogaine, with detectable levels lasting up to 72 hours and an elimination half-life of 10.2 hours. Noribogaine exposure was similar between groups, but the active moiety (ibogaine plus noribogaine) exposure was about 2-fold higher in paroxetine-pretreated subjects. CYP2D6 phenotype correlated strongly with ibogaine AUC and Cmax. The findings suggest genotyping patients before ibogaine treatment and halving the dose in CYP2D6 poor metabolizers to ensure safety.