Influence of prolonged recumbency on drug disposition

Kates, Robert E.; Harapat, Sandra R.; Keefe, Deborah L.; Goldwater, D. J.; Harrison, Donald C.

doi:10.1038/clpt.1980.213

Cited by 30 publications

(19 citation statements)

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“…It is well known that disease and age influence the absorption and disposition of drugs (Sabath, 1970;Palatsi & Kaipainen, 1971;Bolme & Eriksson, 1975;Kunst & Mattie, 1975;George, 1976;Klotz, 1976;Nimmo, 1976;Kates et al, 1980;Welling & Tse, 1982;Yashuara et al, 1982), and these effects probably explain the wide range of the values we obtained in patients as well as the differences between our findings and those of other authors. The relatively high AUCPO we found for both drugs might be partly explained by the differences in the degree of renal dysfunction among our patients, since we found a strong correlation between the plasma clearance and the creatinine clearance of both drugs.…”

Section: Clinical Pharmacokinetic Studycontrasting

confidence: 67%

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

Overbosch¹,

Mattie²,

Furth³

1985

Brit J Clinical Pharma

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1 In this study the antimicrobial effects of phenoxymethylpenicillin (PM) and pheneticillin (PE) in vitro and in an experimental animal infection model were compared as well as the pharmacokinetic properties of both drugs in patients. 2 For the inhibitory effect of PM on short-term (3 h) growth of S. aureus in vitro, this drug was 2.13 times more potent than PE. 3 The protein binding of both drugs was similar (78-80%). 4 The potency ratio of PM to PE against S. aureus in an experimental mouse-thigh infection was only 1.25 to 1. This is explained by the difference in the AUC after subcutaneous administration of PM (0.47 mg 1-1 h) and PE (0.92 mg 1-1 h). 5 The plasma clearance after intravenous administration of PM was 476.4 ml/min and that of PE was 295.1 ml/min; the plasma clearance of both drugs was strongly correlated with the creatinine clearance. 6 The volume of distribution in the steady state of PM was 35.41 and that of PE 22.5 1. 7 In 10 patients, the absorption after oral administration of PM as the acid was 48% and that of the potassium salt of PE was 86% of the dose. 8 From the present results it can be concluded that a difference in effectiveness of different formulations of PM and PE would depend entirely on differences in absorption.

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Section: Clinical Pharmacokinetic Studycontrasting

confidence: 67%

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

Overbosch¹,

Mattie²,

Furth³

1985

Brit J Clinical Pharma

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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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“…Penicillin (10 6 U) or lidocaine (100 mg) was given intravenously before and after 7 days of 0°recumbency. Moreover, during a 4-day head-down tilt [90], we observed variations in the total clearance of lidocaine, obtaining differing results from those of Kates et al [87]. Penicillin was measured by a microbiologic method and lidocaine concentrations were determined by gas chromatography.…”

Section: Human Modelsmentioning

confidence: 65%

“…No data No variation of the clearance after 7 days in supine position [87] Increase in the clearance after 1 and 4 days of )6°bedrest [90] No data Penicillin i.v.…”

Section: Liver Metabolism (Phase I Metabolism)mentioning

confidence: 99%

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The influence of weightlessness on pharmacokinetics

Gandia

Saivin

Houin

2005

Fundamemntal Clinical Pharma

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The primary hostile factor during a spaceflight is the lack of gravity, which can induce space motion sickness and act on bones, muscles and the cardiovascular system. These physiological effects may modify the pharmacokinetics of the drugs administered during the flight producing reduced pharmacological activity or appearance of adverse effects. Given the small number of spaceflights and the difficulties of conducting experiments during missions, pharmacokinetic data obtained in flight are insufficient to determine if drug monitoring is necessary for the drugs present in the onboard medical kit. Therefore, validated earthbound models like tail-suspension performed with animals and long-term bedrest performed with human volunteers are used to simulate weightlessness and to study the pharmacokinetic variations of either absorption, distribution, or elimination of drugs. As a result of these studies, it is possible to make some dosing recommendations but more information is necessary to predict with precision all of the pharmacokinetic variations occurring in spaceflight. To collect more pharmacokinetic information, head-down bedrest studies are still the best solution and as saliva is an appropriate substitution for plasma for some drugs, salivary sampling can be planned during flights.

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Influence of prolonged recumbency on drug disposition

Cited by 30 publications

References 0 publications

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

Influence of posture on pharmacokinetics

The influence of weightlessness on pharmacokinetics

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