Trial reportBritish journal of clinical pharmacology2012
Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects.
Trial report in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- The Impact of Cannabis Use on Cognition in People with HIV: Evidence of Function-Dependent Effects and Mechanisms from Clinical and Preclinical Studies.Current HIV/AIDS reports · 2024Pooled it
- Safety, Tolerability, and Pharmacokinetics of FAAH Inhibitor BIA 10-2474: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Volunteers.Clinical pharmacology and therapeutics · 2022Trial
- Fatty Acid Amide Hydrolase Inhibition by JNJ-42165279: A Multiple-Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers.Clinical and translational science · 2018Trial
- The MOBILE Study-A Phase IIa Enriched Enrollment Randomized Withdrawal Trial to Assess the Analgesic Efficacy and Safety of ASP8477, a Fatty Acid Amide Hydrolase Inhibitor, in Patients with Peripheral Neuropathic Pain.Pain medicine (Malden, Mass.) · 2017Trial
- Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.Drug and alcohol dependence · 2016Trial
- Safety, Tolerability and Pharmacokinetics of FAAH Inhibitor V158866: A Double-Blind, Randomised, Placebo-Controlled Phase I Study in Healthy Volunteers.Drugs in R&D · 2016Trial
- Enhancing anandamide signalling through fatty acid amide hydrolase inhibition: An update on the pharmacological strategy for treating psychiatric disorders.Translational psychiatry · 2026Review
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.Neuropharmacology · 2025Article
- The Role of Fatty Acid Amide Hydrolase, a Key Regulatory Endocannabinoid Enzyme, in Domain-Specific Cognitive Performance in Psychosis.Schizophrenia bulletin · 2025Article
- Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice.bioRxiv : the preprint server for biology · 2025Article
- Mitigation of cisplatin-induced acute kidney injury through oral administration of fatty acid amide hydrolase inhibitor PF-04457845.The Journal of pharmacology and experimental therapeutics · 2025Article
- FAAH inhibitor URB597 shows anti-hyperalgesic action and increases brain and intestinal tissues fatty acid amides in a model of CRFNeurogastroenterology and motility · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.Psychological medicine · 2023Review
- Identification of a novel fatty acid binding protein-5-CB2 receptor-dependent mechanism regulating anxiety behaviors in the prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Endocannabinoid Metabolism and Transport as Drug Targets.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Identifying FAAH Inhibitors as New Therapeutic Options for the Treatment of Chronic Pain through Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2021Article
- On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.Neurotoxicity research · 2021Review
- The endocannabinoid system - current implications for drug development.Journal of internal medicine · 2021Review
- Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses.Frontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledAIMS To evaluate the pharmacology and tolerability of PF-04457845, an orally available fatty acid amide hydrolase-1 (FAAH1) inhibitor, in healthy subjects.
methodsDouble-blind, randomized, placebo-controlled single and multiple rising dose studies and an open-label, randomized, food effect study were conducted. Plasma and urine PF-04457845 concentrations, plasma fatty acid amide concentrations and FAAH1 activity in human leucocytes were measured. Tolerability, including effects on cognitive function, were assessed.
resultsPF-04457845 was rapidly absorbed (median t(max) 0.5-1.2 h). Exposure increased supraproportionally to dose from 0.1 to 10 mg and proportionally between 10 and 40 mg single doses. The pharmacokinetics appeared dose proportional following 14 days once daily dosing between 0.5 and 8 mg. Steady-state was achieved by day 7. Less than 0.1% of the dose was excreted in urine. Food had no effect on PF-04457845 pharmacokinetics. FAAH1 activity was almost completely inhibited (>97%) following doses of at least 0.3 mg (single dose) and 0.5 mg once daily (multiple dose) PF-04457845. Mean fatty acid amide concentrations increased (3.5- to 10-fold) to a plateau and then were maintained following PF-04457845. FAAH1 activity and fatty acid amide concentrations returned to baseline within 2 weeks following cessation of dosing at doses up to 4 mg. There was no evidence of effects of PF-04457845 on cognitive function. PF-04457845, at doses up to 40 mg single dose and 8 mg once daily for 14 days, was well tolerated.
conclusionsPF-04457845 was well tolerated at doses exceeding those required for maximal inhibition of FAAH1 activity and elevation of fatty acid amides.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.