Effects of Posture and Sleep on the Pharmacokinetics of Paracetamol (Acetaminophen) and Its Metabolites

Rumble, Roger; Roberts, Michael S.; Denton, M. J.

doi:10.2165/00003088-199120020-00007

Cited by 30 publications

(30 citation statements)

References 25 publications

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“…The results of Rumble et al on paracetamol suggest that previously reported changes in the volume of distribution do not exist [32]. As a general rule, because distribution is mainly determined by the physico-chemical properties of the administered drug, significant changes due to posture seem unlikely.…”

Section: Effects Of Posture On the Absorption Of Orally Administered mentioning

confidence: 88%

Influence of posture on pharmacokinetics

Queckenberg

Fuhr

2008

Eur J Clin Pharmacol

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Introduction Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion). Objectives Based on a systematic literature search, current data on the effect of posture on physiological characteristics and/or pharmacokinetics are summarized, and the relevance of possible effects, such as those presenting in clinical practice and clinical pharmacokinetic studies, is assessed. Results Postures which favour rapid gastric emptying (sitting, standing, recumbent right) accelerate the absorption of orally administered drugs. Consequently, these postures favour a shorter time to reach peak plasma drug concentration (t max ) and a higher maximum plasma drug concentration (C max ) and-in the case of transient saturation of first-pass metabolism-total exposure (area under the concentration-time curve, AUC) in comparison to recumbent left and supine positions (e.g. nifedipine: AUC 30 and 38% higher in standing and right lateral position vs. left lateral position; C max 149 and 80% higher, respectively). The magnitude of these postural effects depends strongly on the nature and amount of liquids and food ingested before drug administration and is most pronounced in the fasting state and after administration with a nonnutrient liquid. Changes in splanchnic-hepatic blood flow (e.g. reduction of estimated hepatic perfusion by 37% in standing vs. supine position) may substantially affect the metabolism of orally administered drugs, especially of those with a high/saturable first-pass metabolism. For highly protein-bound drugs (e.g. phenytoin, imipramine), the total plasma concentration has been found to be approximately 10% higher in standing than lying subjects due to changes in plasma volume. Conclusions Positioning of a patient may be an effective method of enhancing or retarding absorption of some drugs in appropriate clinical situations (e.g. toxic ingestions, bedridden patients). In clinical pharmacokinetic trials, such as bioequivalence studies, defining and maintaining posture precisely is a useful approach for reducing within-and between-subject variability.Keywords Absorption . Gastric emptying . Pharmacokinetics . Posture IntroductionThe influence of body position on physiological characteristics and pharmacokinetics has been investigated for several decades. The first study on this topic (effects of posture on gastric emptying) was reported to have been performed as early as 1918 [1] when it was observed that barium was emptied faster when subjects lay on the right side compared to other positions. Since then, a multitude of studies has addressed various aspects of postural effects, especially those on gastrointestinal motility, haematological parameters/perfusion and the pharmacokinetics of orally administered drugs.

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Section: Effects Of Posture On the Absorption Of Orally Administered mentioning

confidence: 88%

Influence of posture on pharmacokinetics

Queckenberg

Fuhr

2008

Eur J Clin Pharmacol

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“…The effects on the pharmacokinetics and bioavailability of acetaminophen of such factors as the age [1,2] and sex [1,3] of patients, the excess of body mass [3], the condition of gastro-intestinal tract peristalsis, simultaneous administration with various foods [4,5], and type of motor activity (including prolonged anti-orthostatic hypokinesia) and sleep [6,7] are currently widely studied.…”

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confidence: 99%

Pharmacokinetics of acetaminophen administered in tablets and capsules under long-term space flight conditions

et al. 2009

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The pharmacokinetics of acetaminophen in two medicinal forms, tablets and capsules, have been studied in healthy volunteers after single peroral administration at a dose of 500 mg under usual living conditions and during long-term space flight. The rate of drug absorption from tablets decreases significantly whereas the relative bioavailability increases substantially under microgravity conditions (compared with usual conditions). For the encapsulated medicinal form, the time of absorption decreases statistically reliably and the half-elimination time, the average retention time, and the distribution volume increase considerably whereas the bioavailability changes insignificantly.The onset of a clinical effect and its strength and duration through any administration pathway depend on the bioavailability of the drug. The effects on the pharmacokinetics and bioavailability of acetaminophen of such factors as the age [1, 2] and sex [1, 3] of patients, the excess of body mass [3], the condition of gastro-intestinal tract peristalsis, simultaneous administration with various foods [4,5], and type of motor activity (including prolonged anti-orthostatic hypokinesia) and sleep [6,7] are currently widely studied.Factors such as weightlessness, changes of water-salt balance, mineral saturation of bone, hematological changes, reduction of immunological reactivity, functional changes of neuropsychic status and gastro-intestinal system, etc. are known to have a negative effect on the human organism during long-term space flight. However, the actual trends in the pharmacokinetics of various drugs (including acetaminophen) during long-term space flight are practically unstudied and are very critical because the probability of developing acute diseases and damage increases during planned longterm orbital and interplanetary flights. This requires the use of drugs to correct these maladies. EXPERIMENTAL PARTThe pharmacokinetic investigation involved 10 healthy men (members of the ISS space expeditions) who were divided into two groups of 5 men.The average age in the first group, i.e., those administered the tablet form of acetaminophen, was 44.6 yr (from 39 to 50 yr); in the second group, i.e., those administered encapsulated acetaminophen, 44.4 yr (from 40 to 47 yr).The study procedure and method were approved beforehand by the Commission on Biomedical Ethics of the IMBP RAS. Informed consent was obtained from the volunteers for the space experiment.The pharmacokinetics and bioavailability of the acetaminophen drug forms were studied using its concentration dynamics in saliva because obtaining blood samples under microgravity conditions is difficult and the ability to study acetaminophen pharmacokinetics from its distribution dynamics in saliva had been demonstrated previously [8,9], including during space flights [10].The pharmacokinetics of acetaminophen were studied first approximately two months before the start of the space flight (SF) using the standard protocol.Volunteers were prohibited from taking any drugs, including vi...

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“…Thus, studies of the effect of motor activity on acetaminophen pharmacokinetics [5] found that the pharmacokinetic parameters of the drug changed insignificantly during sleep and bed rest with the execption of MRT, which decreased. Apparently these effects are due to not only a limitation on motor activity but also changes of hemodynamics under ANOH conditions and the neutralizing effect of acetaminophen on glomerular filtration under ANOH conditions.…”

Section: Resultsmentioning

confidence: 99%

Effect of antiorthostatic hypokinesia on acetaminophen pharmacokinetics and its distribution in saliva of healthy volunteers

et al. 2009

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The pharmacokinetics of acetaminophen in a group of healthy volunteers has been studied after a single peroral administration at a dose of 625 mg under normal and antiorthostatic hypokinesia (head-down bed rest) conditions. A highly significant correlation has been established between the concentrations of acetaminophen in the blood plasma and saliva of volunteers and also between the pharmacokinetic parameters calculated from the dynamics of drug distribution in plasma and saliva. A tendency toward increased concentration of acetaminophen in saliva compared to blood plasma of volunteers; decreased time of attaining the maximum drug concentration, relative bioavailability, time of half-elimination, and mean retention time in the organism; and increased general clearance has been observed.

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Effects of Posture and Sleep on the Pharmacokinetics of Paracetamol (Acetaminophen) and Its Metabolites

Cited by 30 publications

References 25 publications

Influence of posture on pharmacokinetics

Influence of posture on pharmacokinetics

Pharmacokinetics of acetaminophen administered in tablets and capsules under long-term space flight conditions

Effect of antiorthostatic hypokinesia on acetaminophen pharmacokinetics and its distribution in saliva of healthy volunteers

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