2016
DOI: 10.1111/bcp.13127
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Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects

Abstract: AIMTo evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. METHODSSingle (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass index 24.8 ± 3.1 kg m -2 [mean ± standard deviation]) received ≥1 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF-05190457 and/or placebo in the SAD. In the MAD stud… Show more

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Cited by 43 publications
(40 citation statements)
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“…However, results in human trials are less favourable with no difference in weight between obese patients receiving ghrelin immunisation over 20 weeks, with both active and control groups losing 3.6 kg weight [92]. We were unable to identify any current clinical trials exploring ghrelin antagonism under progress, though recently ghrelin receptor inverse agonists have been successfully profiled in humans [93].…”
Section: Ghrelin Vaccines and Antagonistsmentioning
confidence: 99%
“…However, results in human trials are less favourable with no difference in weight between obese patients receiving ghrelin immunisation over 20 weeks, with both active and control groups losing 3.6 kg weight [92]. We were unable to identify any current clinical trials exploring ghrelin antagonism under progress, though recently ghrelin receptor inverse agonists have been successfully profiled in humans [93].…”
Section: Ghrelin Vaccines and Antagonistsmentioning
confidence: 99%
“…These results suggest that the ghrelin receptor agonist may be used for patients with chronic kidney diseases and symptomatic gastroparesis in the future, but more clinical studies are still needed. In pharmacokinetics and pharmacodynamics of the clinical trial, ghrelin receptor inverse agonists acutely block the ghrelin receptor in healthy volunteers and dose-dependently increase heart rate, delay gastric emptying, and induce somnolence [ 60 ]. Unacylated ghrelin analog is well tolerated in humans and exhibits metabolic benefits in overweight/obese and T2DM subjects [ 61 ].…”
Section: Function Of Ghrelin and Its Receptormentioning
confidence: 99%
“…Antagonizing or blocking the effects of AG on food intake, body weight and glucose metabolism has emerged in the past decade as an attractive pharmaco-therapeutic target. Antagonists and inverse agonists of the AG receptor GHSR, as well as AG-blocking agents have been designed to this end, but mixed results have been obtained so far in animal models while clinical efficacy data are lacking ([ 26 , 27 ]). On the other hand, inhibitors of the Ghrelin O-Acyltransferase (GOAT) enzyme responsible for acylation are still at an early stage of investigation and no efficacy data is available [ 27 ].…”
Section: Introductionmentioning
confidence: 99%