Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers

Neha Parikh,1 William G Kramer,2 Varun Khurana,1 Christina Cognata Smith,1 Santosh Vetticaden,1 1INSYS Therapeutics, Inc., Chandler, AZ, USA; 2Kramer Consulting LLC, North Potomac, MD, USA Background: Dronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an ora...

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Autores principales:	Parikh N, Kramer WG, Khurana V, Cognata Smith C, Vetticaden S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	pharmacokinetics delta 9-tetrahydrocannabinol safety variability Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4aa8035f493d4609a16cbffdcaf6e2b2
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spelling	oai:doaj.org-article:4aa8035f493d4609a16cbffdcaf6e2b22021-12-02T07:10:35ZBioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers1179-1438https://doaj.org/article/4aa8035f493d4609a16cbffdcaf6e2b22016-10-01T00:00:00Zhttps://www.dovepress.com/bioavailability-study-of-dronabinol-oral-solution-versus-dronabinol-ca-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Neha Parikh,1 William G Kramer,2 Varun Khurana,1 Christina Cognata Smith,1 Santosh Vetticaden,1 1INSYS Therapeutics, Inc., Chandler, AZ, USA; 2Kramer Consulting LLC, North Potomac, MD, USA Background: Dronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an oral capsule. This study evaluated the bioavailability of a new formulation, dronabinol oral solution, versus a dronabinol capsule formulation. Methods: In an open-label, four-period, single-dose, crossover study, healthy volunteers were randomly assigned to one of two treatment sequences (T-R-T-R and R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsule) under fasted conditions, with a minimum 7-day washout period between doses. Analyses were performed on venous blood samples drawn 15 minutes to 48 hours postdose, and dronabinol concentrations were assayed by liquid chromatography–tandem mass spectrometry. Results: Fifty-one of 52 individuals had pharmacokinetic data for analysis. The 90% confidence interval of the geometric mean ratio (oral solution/capsule) for dronabinol was within the 80%–125% bioequivalence range for area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–t) and AUC from time zero to infinity (AUC0–∞). Maximum plasma concentration was also bioequivalent for the two dronabinol formulations. Intraindividual variability in AUC0–∞ was >60% lower for dronabinol oral solution 4.25 mg versus dronabinol capsule 5 mg. Plasma dronabinol concentrations were detected within 15 minutes postdose in 100% of patients when receiving oral solution and in <25% of patients when receiving capsules. Conclusion: Single-dose dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsule 5 mg under fasted conditions. Dronabinol oral solution formulation may provide an easy-to-swallow administration option with lower intraindividual variability as well as more rapid absorption versus dronabinol capsules. Keywords: pharmacokinetics, Δ-9-tetrahydrocannabinol, safety, variabilityParikh NKramer WGKhurana VCognata Smith CVetticaden SDove Medical Pressarticlepharmacokineticsdelta 9-tetrahydrocannabinolsafetyvariabilityTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 8, Pp 155-162 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	pharmacokinetics delta 9-tetrahydrocannabinol safety variability Therapeutics. Pharmacology RM1-950
spellingShingle	pharmacokinetics delta 9-tetrahydrocannabinol safety variability Therapeutics. Pharmacology RM1-950 Parikh N Kramer WG Khurana V Cognata Smith C Vetticaden S Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
description	Neha Parikh,1 William G Kramer,2 Varun Khurana,1 Christina Cognata Smith,1 Santosh Vetticaden,1 1INSYS Therapeutics, Inc., Chandler, AZ, USA; 2Kramer Consulting LLC, North Potomac, MD, USA Background: Dronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an oral capsule. This study evaluated the bioavailability of a new formulation, dronabinol oral solution, versus a dronabinol capsule formulation. Methods: In an open-label, four-period, single-dose, crossover study, healthy volunteers were randomly assigned to one of two treatment sequences (T-R-T-R and R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsule) under fasted conditions, with a minimum 7-day washout period between doses. Analyses were performed on venous blood samples drawn 15 minutes to 48 hours postdose, and dronabinol concentrations were assayed by liquid chromatography–tandem mass spectrometry. Results: Fifty-one of 52 individuals had pharmacokinetic data for analysis. The 90% confidence interval of the geometric mean ratio (oral solution/capsule) for dronabinol was within the 80%–125% bioequivalence range for area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–t) and AUC from time zero to infinity (AUC0–∞). Maximum plasma concentration was also bioequivalent for the two dronabinol formulations. Intraindividual variability in AUC0–∞ was >60% lower for dronabinol oral solution 4.25 mg versus dronabinol capsule 5 mg. Plasma dronabinol concentrations were detected within 15 minutes postdose in 100% of patients when receiving oral solution and in <25% of patients when receiving capsules. Conclusion: Single-dose dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsule 5 mg under fasted conditions. Dronabinol oral solution formulation may provide an easy-to-swallow administration option with lower intraindividual variability as well as more rapid absorption versus dronabinol capsules. Keywords: pharmacokinetics, Δ-9-tetrahydrocannabinol, safety, variability
format	article
author	Parikh N Kramer WG Khurana V Cognata Smith C Vetticaden S
author_facet	Parikh N Kramer WG Khurana V Cognata Smith C Vetticaden S
author_sort	Parikh N
title	Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
title_short	Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
title_full	Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
title_fullStr	Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
title_full_unstemmed	Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
title_sort	bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/4aa8035f493d4609a16cbffdcaf6e2b2
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Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers

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