Effect of exercise on disposition and pharmacokinetics of drugs

Somani, Satu M.; Gupta, Sundeep; Frank, Stuart; Corder, Clinton N.

doi:10.1002/ddr.430200302

Cited by 28 publications

(14 citation statements)

References 130 publications

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“…This represents a pitfall in the prediction of drug pharmacokinetics for those compounds which may demonstrate this phenomenon. Somani et al (1990) revealed that exercise has the tendency to either have no effect on or reduce the distribution volume of many drugs, a result mirrored by our simulations. Heat exposure appears to have a negligible effect on the volume of distribution of drugs, based on a review by Vanakoski and Seppälä (1998), which is the case for a number of simulated scenarios, but not all (Fig.…”

Section: Discussionsupporting

confidence: 65%

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

Sidhu

Peng

Cheung

et al. 2011

Can. J. Physiol. Pharmacol.

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Under extreme conditions of heat exposure and exercise stress, the human body undergoes major physiological changes. Perturbations in organ blood flows, gastrointestinal properties, and vascular physiology may impact the body's ability to absorb, distribute, and eliminate drugs. Clinical studies on the effect of these stressors on drug pharmacokinetics demonstrate that the likelihood of pharmacokinetic alteration is dependent on drug properties and the intensity of the stressor. The objectives of this study were to use literature data to quantify the correlation between exercise and heat exposure intensity to changing physiological parameters and further, to use this information for the parameterization of a whole-body, physiologically based pharmacokinetic model for the purposes of determining those drug properties most likely to demonstrate altered drug pharmacokinetics under stress. Cardiac output and most organ blood flows were correlated with heart rate using regression analysis. Other altered parameters included hematocrit and intravascular albumin concentration. Pharmacokinetic simulations of intravenous and oral administration of hypothetical drugs with either a low or high value of lipophilicity, unbound fraction in plasma, and unbound intrinsic hepatic clearance demonstrated that the area under the curve of those drugs with a high unbound intrinsic clearance was most affected (up to a 130% increase) following intravenous administration, whereas following oral administration, pharmacokinetic changes were smaller (<40% increase in area under the curve) for all hypothetical compounds. A midazolam physiologically based pharmacokinetic model was also used to demonstrate that simulated changes in pharmacokinetic parameters under exercise and heat stress were generally consistent with those reported in the literature.

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Section: Discussionsupporting

confidence: 65%

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

Sidhu

Peng

Cheung

et al. 2011

Can. J. Physiol. Pharmacol.

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“…Caffeine CL is independent of HBF [8,10] and under normal (sea level) conditions its metabolism can only be modified by changes in enzyme activity [4]. The results from this study indicate that there was a significant increase in the paraxanthine to caffeine and total MET to caffeine ratios ( Table 2) following exposure to altitude.…”

Section: Discussionsupporting

confidence: 55%

“…Indocyanine Green is a tricarbocyanine dye which is classified as a capacity limited drug [10,14]. It rapidly binds to the plasma proteins and is distributed into the plasma volume.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, the ratio of the concentration of its primary metabolities (theobromine, theophylline, and paraxanthine) to caffeine can be used to examine its rate of metabolism [3,4,8]. In contrast, ICG is a flow dependent drug which undergoes no metabolism and is removed exclusively by the liver [9,10]. Although the miniature swine is an acceptable model for drug studies it is well accepted that there are species differences in the metabolism of drugs like caffeine [7].…”

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confidence: 99%

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Effects of altitude (4300 M) on the pharmacokinetics of caffeine and cardio-green in humans

Kamimori

Eddington

Hoyt

et al. 1995

Eur J Clin Pharmacol

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The effects of chronic exposure to high altitude on the pharmacokinetics of caffeine and cardio-green (ICG) were examined in eight healthy males (23-35 y) at sea level (SEA) and following 16 days residence at 4300 m (ALT). ICG (0.5 mg. kg-1) was administered as an intravenous bolus and caffeine (4 mg. kg-1) in an orally ingested solution. The concentration of ICG, caffeine, and the primary metabolites of caffeine (MET) were determined in serial blood samples and their pharmacokinetics computed. In comparison to SEA, ALT resulted in a significant decrease in a caffeine half-life (t1/2, 4.7 vs 6.7 h) and area under the curve (2.5 vs 3.7 g.l-1.min-1), and increased clearance (117 vs 86 ml.min-1.70 kg-1). In ALT the area under the curve the ICG significantly decreased (85 vs 207 mg.l-1.min-1) and the volume of distribution and clearance increased (5.2 vs 2.4 l and 532 vs 234 ml.min-1 respectively) compared to SEA. There was a significant increase in the AUC ratio of MET to caffeine indicating that either metabolite formation or elimination was increased in ALT. These results demonstrate that in humans, chronic exposure to 4300 m results in the modification of the pharmacokinetics of caffeine and ICG.

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“…To explore the possible influence of exercise on the DT as obtained under the EHSLC conditions, the aim of the present study was to compare the kinetic disposition of 2 test drugs in rest conditions and in conditions involving a 3 h endurance‐type exercise. As it has been reported that exercise decreases the distribution and excretion of flow‐limited drugs and increases the distribution and excretion of capacity‐limited drugs (Somani et al. 1990), dexamethasone, a drug having a rather high clearance rate and phenylbutazone, a drug with a low clearance rate, were selected as test drugs.…”

Section: Introductionmentioning

confidence: 99%

Effect of an endurance‐like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: Application to medication control

Authie

Garcia

Popot

et al. 2010

Equine Veterinary Journal

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Establishing DTs or withdrawal times (WTs) are relevant as plasma and urine half-lives, but not clearance, are the main determinants of DT length. Veterinarians may realistically decide upon a WT for a legitimate drug based on the corresponding DT obtained under resting conditions providing this drug has a low hepatic extraction ratio and a safety margin is added to allow for all possible sources of variability.

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Effect of exercise on disposition and pharmacokinetics of drugs

Abstract: INTRODUCTION

Cited by 28 publications

References 130 publications

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

Effects of altitude (4300 M) on the pharmacokinetics of caffeine and cardio-green in humans

Effect of an endurance‐like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: Application to medication control

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