Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat

Sassenbroeck, Diederik K. Van; Paepe, Peter De; Belpaire, Frans; Boon, Paul; Buylaert, Walter

doi:10.1097/00000542-200211000-00027

Cited by 8 publications

(1 citation statement)

References 27 publications

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“…Van Sassenbroeck et al looked at the effect of hypovolemia (30% of blood volume) on the pharmacokinetics of gamma-hydroxybutyrate (GHB) in rats (53). This study is especially relevant because GHB and ethanol have similar pharmacokinetic properties, including distribution volumes (54).…”

Section: Introductionmentioning

confidence: 99%

Impact of Trauma, Massive Blood Loss and Administration of Resuscitation Fluids on a Person's Blood-Alcohol Concentration and Rate of Ethanol Metabolism

Jones

2016

Academic Forensic Pathology

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Excessive drinking and drunkenness are tightly linked to many types of intentional and unintentional injuries involving trauma and blood loss, which often necessitate emergency medical intervention. This article considers the impact of trauma, massive blood loss, and the administration of life-saving replacement fluids on a person's blood alcohol concentration (BAC) and rate of ethanol metabolism. Both German and English language journals were reviewed and results from animal experiments, human studies, and actual victims of trauma undergoing life-saving treatment were considered. If trauma-related bleeding occurs when some ingested alcohol remains unabsorbed in the stomach, then under these circumstances continued absorption into portal venous blood is delayed, owing to altered splanchnic circulation. Hemodilution caused by administration of replacement fluids has only minimal effects on a preexisting BAC, because ethanol distributes into the total body water (TBW) compartment, which represents 50-60% of body weight. After hypovolemia there is a transfer of fluids from tissue compartments into the blood, which becomes more like plasma in composition with lower hematocrit and hemoglobin content. Unless the trauma or emergency treatment impedes hepatic blood flow, the rate of ethanol metabolism is not expected to differ from normal values, namely 0.10-0.25 g/L/h (0.01-0.025 g% per h). If ethanol is fully absorbed and distributed in all body fluids and tissues, neither massive blood loss nor administration of resuscitating fluids is expected to have any significant effect on a preexisting BAC or the rate of ethanol metabolism.

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Section: Introductionmentioning

confidence: 99%

Impact of Trauma, Massive Blood Loss and Administration of Resuscitation Fluids on a Person's Blood-Alcohol Concentration and Rate of Ethanol Metabolism

Jones

2016

Academic Forensic Pathology

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Model Informed Pediatric Development Applied to Bilastine: Ontogenic PK Model Development, Dose Selection for First Time in Children and PK Study Design

Vozmediano¹,

Sologuren

Lukas³

et al. 2017

Pharm Res

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Integration of preclinical and clinical knowledge to predict intravenous PK in human: Bilastine case study

Vozmediano¹,

Ortega

Lukas³

et al. 2013

Eur J Drug Metab Pharmacokinet

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Modern pharmacometrics can integrate and leverage all prior proprietary and public knowledge. Such methods can be used to scale across species or comparators, perform clinical trial simulation across alternative designs, confirm hypothesis and potentially reduce development burden, time and costs. Crucial yet typically lacking in integration is the pre-clinical stage. Prediction of PK in man, using in vitro and in vivo studies in different animal species, is increasingly well theorized but could still find wider application in drug development. The aim of the present work was to explore methods for bridging pharmacokinetic knowledge from animal species (i.v. and p.o.) and man (p.o.) into i.v. in man using the antihistamine drug bilastine as example. A model, predictive of i.v. PK in man, was developed on data from two pre-clinical species (rat and dog) and p.o. in man bilastine trials performed earlier. In the knowledge application stage, two different approaches were used to predict human plasma concentration after i.v. of bilastine: allometry (several scaling methods) and a semi-physiological method. Both approaches led to successful predictions of key i.v. PK parameters of bilastine in man. The predictive i.v. PK model was validated using later data from a clinical study of i.v. bilastine. Introduction of such knowledge in development permits proper leveraging of all emergent knowledge as well as quantification-based exploration of PK scenario, e.g. in special populations (pediatrics, renal insufficiency, comedication). In addition, the methods permit reduction or elimination and certainly optimization of learning trials, particularly those concerning alternative off-label administration routes.

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Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat

Cited by 8 publications

References 27 publications

Impact of Trauma, Massive Blood Loss and Administration of Resuscitation Fluids on a Person's Blood-Alcohol Concentration and Rate of Ethanol Metabolism

Impact of Trauma, Massive Blood Loss and Administration of Resuscitation Fluids on a Person's Blood-Alcohol Concentration and Rate of Ethanol Metabolism

Model Informed Pediatric Development Applied to Bilastine: Ontogenic PK Model Development, Dose Selection for First Time in Children and PK Study Design

Integration of preclinical and clinical knowledge to predict intravenous PK in human: Bilastine case study

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