PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers

Atsmon, Jacob; Cherniakov, Irina; Izgelov, Dvora; Hoffman, Amnon; Deutsch, Lisa; Deutsch, Frederic; Heffetz, Daphna; Sacks, Hagit

doi:10.1016/j.xphs.2017.12.020

Cited by 80 publications

(57 citation statements)

References 28 publications

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“…The absorption kinetics among oral capsule studies were highly variable. The variability may be explained by the various capsule formulations that were included in our study . Feeding status may also contribute to the variability of absorption kinetics among oral capsule studies.…”

Section: Discussionmentioning

confidence: 99%

“…The variability may be explained by the various capsule formulations that were included in our study. 11,13,17,[21][22][23][24] Feeding status may also contribute to the variability of absorption kinetics among oral capsule studies. The presence of food, especially with high-fat content, may slow gastric emptying and gastrointestinal (GI) motility, and therefore delay drug absorption and reduce Cmax.…”

Section: Discussionmentioning

confidence: 99%

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Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

2020

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Introduction There is a large variation in cannabidiol (CBD) pharmacokinetics and little information on its bioavailability. This study aims to establish the CBD dose‐exposure relationship and to evaluate the effects of dosage forms, food, and doses on CBD absorption. Methods Single‐dose (range: 5–6000 mg) CBD plasma concentration‐time profiles administered as oral solution (OS), oral capsule (OC), or oromucosal spray/drop (OM) from healthy volunteers were extracted from 15 published clinical studies. A dose‐exposure proportionality assessment was performed, and a population‐based meta‐analysis of CBD pharmacokinetics and systemic bioavailability was conducted with a nonlinear mixed‐effects modeling. A three‐compartment model with a Weibull or zero‐order absorption model was used to describe CBD disposition and absorption kinetics. Dosage form, food, and dose were assessed for covariation. Results Oral solution CBD exposures increased less than proportionally with doses of 750 mg or greater, and bioavailability (6.5% at 3000 mg) decreased with increasing dose. The bioavailability of OC (5.6%) and fed‐state OM (6.2%) were similar, whereas it was lower in fasted‐state OM (0.9%). The Weibull absorption model best described OS, OC, and fed‐state OM profiles. The slowest absorption rate was observed in OS, resulting in a time of maximum concentration of 4.75 hours, followed by fed‐state OM (3.13 hrs) and OC (2.1 hrs). The absorption kinetics of fasted‐state OM was best described by a zero‐order absorption for the duration of 1.71 hours. Conclusion The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

2020

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“…Purified CBD preparations increase serum levels in a dose-dependent manner ( 33 ). However, pharmacokinetics of different CBD preparations or different routes of application and correlations between CBD serum level and anti-seizure effects or side effects have not been fully established ( 36 , 37 ). Accordingly, almost none of the participants measure CBD serum levels.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol for Treatment of Childhood Epilepsy–A Cross-Sectional Survey

et al. 2018

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Background: The interest in cannabidiol (CBD) for treatment of epilepsy has been increasing over the last years. However, practitioner's attitudes concerning the use of CBD for epilepsy treatment appears to be divided and data about its clinical use in daily practice are not available.Objective: To improve the knowledge about the current use of CBD amongst European practitioners treating children and adolescents for epilepsy.Methods: Cross-sectional survey using an open-access online questionnaire for physicians treating children or adolescents for epilepsy within eight European countries from December 2017 to March 2018.Results: One-hundred fifty-five physicians participated in the survey. CBD is increasingly used by 45% (69/155) of participants, treating a mean (range) number of 3 (1–35) with CBD. Only 48% of the participants prescribing CBD are exclusively using purified CBD to treat children and adolescents with epilepsy, the remainder also applies preparations containing delta9-tetrahydrocannabinol (THC). Reported daily CBD doses range from < 10 to 50 mg/kg body weight. Management of CBD therapy in regard of monitoring side effects and adjusting concomitant therapy differs widely amongst participants. Their primary objective for commencing CBD is improving patient's quality of life. Participants frequently receive inquiries about CBD treatment but only 40% may actively suggest CBD as a treatment option. Of the 85 participants currently not using CBD for epilepsy treatment, 70% would consider using CBD if available in their country of practice or given the opportunity to become familiar with this treatment option.Conclusions: CBD is increasingly used by participating physicians but individual experience remains limited. There are very diverse opinions about the use of CBD to treat epilepsy in children and adolescents and widely differing views on how to manage the CBD treatment.

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“…PTL401, based on a self-emulsifying drug delivery system, aimed at avoiding the "first pass" effect, was developed by Cherniakov and collaborators [114]. Accordingly, the PTL401 product yielded 1.6-fold higher maximum plasma concentration than the equivalent dose of a reference commercial product (Sativex ® , oromucosal spray), for both cannabinoid active principles.…”

Section: An Oral Formulation Of Thc and Cbd-ptl401mentioning

confidence: 99%

Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy

et al. 2020

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Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography–mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.

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PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers

Cited by 80 publications

References 28 publications

Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

Model‐Based Analysis of Cannabidiol Dose‐Exposure Relationship and Bioavailability

Cannabidiol for Treatment of Childhood Epilepsy–A Cross-Sectional Survey

Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy

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