The effect of posture on the pharmacokinetics of intravenous benzylpenicillin

Rumble, Roger; Roberts, Michael S.; Scott, A. R.

doi:10.1007/bf00608225

Cited by 16 publications

(12 citation statements)

References 10 publications

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“…Several studies failed to show any relevant postural effect on metabolism or elimination of the drugs administered intravenously [44][45][46][47]. As there is no absorption phase after intravenous application, the effects of posture on gastric emptying are not relevant.…”

Section: Posture and Route Of Administrationmentioning

confidence: 99%

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: Posture and Route Of Administrationmentioning

confidence: 99%

Influence of posture on pharmacokinetics

Queckenberg

Fuhr

2008

Eur J Clin Pharmacol

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“… and the experimental data from ref. . In the original simulations, the physiology‐related parameters (e.g., Q CO , Q HEP , BW, V p ) were kept constant to the literature values, whereas drug‐specific parameters (e.g., K p , CL intu /nh, f d ) were optimized based on the PK data.…”

Section: Atlas Mpbpk Simulationsmentioning

confidence: 99%

ATLAS mPBPK: A MATLAB‐Based Tool for Modeling and Simulation of Minimal Physiologically‐Based Pharmacokinetic Models

Mavroudis

Ayyar

Jusko

2019

CPT Pharmacom & Syst Pharma

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Minimal physiologically‐based pharmacokinetic ( mPBPK ) models are frequently used to model plasma pharmacokinetic (PK) data and utilize and yield physiologically relevant parameters. Compared with classical compartment and whole‐body physiologically‐based pharmacokinetic modeling approaches, mPBPK models maintain a structure of intermediate physiological complexity that can be adequately informed by plasma PK data. In this tutorial, we present a MATLAB ‐based tool for the modeling and simulation of mPBPK models ( ATLAS mPBPK ) of small and large molecules. This tool enables the users to perform the following: (i) PK data visualization, (ii) simulation, (iii) parameter optimization, and (iv) local sensitivity analysis of mPBPK models in a simple and efficient manner. In addition to the theoretical background and implementation of the different tool functionalities, this tutorial includes simulation and sensitivity analysis showcases of small and large molecules with and without target‐mediated drug disposition.

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“…I feel certain that exercise (subjects were allowed to walk whilst in the upright position) possibly added to the postural effect of an increase in real blood flow and higher active renal secretion of amoxicillin. We did not find differences when we examined benzyl penicillin given intramuscularly [20] or intravenously [21]. Lying down and sleeping had the effect of delaying the absorption of paracetamol [22].…”

Section: Physiological Pharmacokineticsmentioning

confidence: 99%

Drug structure–transport relationships

Roberts

2010

J Pharmacokinet Pharmacodyn

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Malcolm Rowland has greatly facilitated an understanding of drug structure–pharmacokinetic relationships using a physiological perspective. His view points, covering a wide range of activities, have impacted on my own work and on my appreciation and understanding of our science. This overview summarises some of our parallel activities, beginning with Malcolm’s work on the pH control of amphetamine excretion, his work on the disposition of aspirin and on the application of clearance concepts in describing the disposition of lidocaine. Malcolm also spent a considerable amount of time developing principles that define solute structure and transport/pharmacokinetic relationships using in situ organ studies, which he then extended to involve the whole body. Together, we developed a physiological approach to studying hepatic clearance, introducing the convection–dispersion model in which there was a spread in blood transit times through the liver accompanied by permeation into hepatocytes and removal by metabolism or excretion into the bile. With a range of colleagues, we then further developed the model and applied it to various organs in the body. One of Malcolm’s special interests was in being able to apply this knowledge, together with an understanding of physiological differences in scaling up pharmacokinetics from animals to man. The description of his many other activities, such as the development of clearance concepts, application of pharmacokinetics to the clinical situation and using pharmacokinetics to develop new compounds and delivery systems, has been left to others.

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The effect of posture on the pharmacokinetics of intravenous benzylpenicillin

Cited by 16 publications

References 10 publications

Influence of posture on pharmacokinetics

Influence of posture on pharmacokinetics

ATLAS mPBPK: A MATLAB‐Based Tool for Modeling and Simulation of Minimal Physiologically‐Based Pharmacokinetic Models

Drug structure–transport relationships

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