Evidence map›Paper›PMID 26893218›Full record

ArticleThe AAPS journal2016

The Population Pharmacokinetics of D-β-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate.

Vittal Shivva, Pete J Cox, Kieran Clarke, Richard L Veech, Ian G Tucker, Stephen B Duffull

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Vittal ShivvaSchool of Pharmacy, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand. vittal.shivva@otago.ac.nz.
Pete J CoxDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Kieran ClarkeDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Richard L VeechLaboratory of Metabolic Control, NIAAA/NIH, Rockville, Maryland, USA.
Ian G TuckerSchool of Pharmacy, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand.
Stephen B DuffullSchool of Pharmacy, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand.
University of Otago · NZUniversity of Oxford · GBNational Institute on Alcohol Abuse and Alcoholism · US

Funding

Metabolic Control AnalysisZIAAA000110 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI VEECH, RICHARD L · 2009 to 2020
$17.2M
6 · The paper itself

Abstract

The administration of ketones to induce a mild ketosis is of interest for the alleviation of symptoms associated with various neurological disorders. This study aimed to understand the pharmacokinetics (PK) of D-β-hydroxybutyrate (BHB) and quantify the sources of variability following a dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester). Healthy volunteers (n = 37) were given a single drink of the ketone monoester, following which, 833 blood BHB concentrations were measured. Two formulations and five dose levels of ketone monoester were used. A nonlinear mixed effect modelling approach was used to develop a population PK model. A one compartment disposition model with negative feedback effect on endogenous BHB production provided the best description of the data. Absorption was best described by two consecutive first-order inputs and elimination by dual processes involving first-order (CL = 10.9 L/h) and capacity limited elimination (V max = 4520 mg/h). Covariates identified were formulation (on relative oral bioavailable fraction and absorption rate constant) and dose (on relative oral bioavailable fraction). Lean body weight (on first-order clearance) and sex (on apparent volume of distribution) were also significant covariates. The PK of BHB is complicated by complex absorption process, endogenous production and nonlinear elimination. Formulation and dose appear to strongly influence the kinetic profile following ketone monoester administration. Further work is needed to quantify mechanisms of absorption and elimination of ketones for therapeutic use in the form of ketone monoester.

Indexed as

FemaleHumansHydroxybutyratesMaleModels, TheoreticalHydroxybutyratesD-β-hydroxybutyrateexogenous ketosisketone monoesterpharmacokineticspopulation models

Identifiers

PMID26893218
PMCPMC5256599
OpenAlexW2281906723

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.