Clinical pharmacology in drug development
November 1, 2016
Paul Glue, Gavin Cape, Donna Tunnicliff et al.
66 citations
Noribogaine, the active metabolite of ibogaine, was tested for the first time in patients on methadone opioid substitution therapy. In a randomized, double-blind, placebo-controlled trial with 27 patients, doses of 60, 120, or 180 mg were well tolerated, with common side effects including temporary changes in light perception, headache, and nausea. The drug showed dose-linear increases in blood concentration and a slow elimination half-life of 24–30 hours. Noribogaine caused a concentration-dependent increase in heart rate–corrected QT interval (QTcI), with average increases of about 16, 28, and 42 milliseconds at the three doses. There was a nonstatistically significant trend toward reduced opioid withdrawal symptoms, most notably at 120 mg, but study design issues may have affected results.
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.
Therapeutic Advances in Psychopharmacology
January 1, 2020
P. Glue, N. Medlicott, Shona Neehoff et al.
43 citations
An extended-release oral ketamine tablet was tested in seven patients with treatment-resistant depression and anxiety who had previously responded to subcutaneous ketamine. Over 96 hours, all patients showed more than 50% improvement in mood ratings, with gradual reductions in anxiety and depression. The tablet was safe and well tolerated, with no changes in vital signs and only one brief report of dissociation. The ratio of norketamine to ketamine increased over time, suggesting ketamine may induce its own metabolism. Serum BDNF concentrations did not change. The findings suggest extended-release oral ketamine may improve safety and tolerability while offering a slightly delayed onset of mood improvement compared to injected forms.