Posture and theophylline kinetics.

Warren, J. B.; Cuss, Francis M.; Barnes, Peter J.

doi:10.1111/j.1365-2125.1985.tb02701.x

Cited by 43 publications

(18 citation statements)

References 9 publications

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“…More recently, an attempt has been made at investigating the effect of posture on single dose pharmacokinetics of a slow release aminophylline preparation, Phyllocontin (Warren et al, 1985). Whilst not proven, this effect might be capable of explaining the circadian variation in both 75 Z x , E predose concentrations and tmax seen during chronic dosing.…”

Section: Resultsmentioning

confidence: 99%

Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing.

Jackson

Johnston

Woollard

et al. 1988

Brit J Clinical Pharma

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1. Eight volunteers were given seven doses of 200 mg of slow release theophylline at either 11.00 h and 23.00 h (regimen 1) or 17.00 h and 05.00 h (regimen 2). At the time of the sixth dose (60 h) hourly blood sampling was started and continued for 24 h. After at least 1 week volunteers crossed over to the other regimen. 2. Volunteers retired to bed at 23.00 h and arose after the 07.00 h sample during both regimens. 3. During regimen 1 there was a marked rise in mean tmax from 3.3 h after dosing at 11.00 h to 9.3 h after dosing at 23.00 h (P less than 0.001). There was also a fall in AUC(0,12) from 89.9 mg l‐1 h after dosing at 11.00 h to 79.0 mg l‐1 h after dosing at 23.00 h. There was no difference in mean Cmax values. 4. During regimen 2 these circadian changes were abolished with mean values after both dosing times lying between those observed during regimen 1. 5. A marked delay in absorption occurs at night and cannot be explained by food intake.

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Section: Resultsmentioning

confidence: 99%

Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing.

Jackson

Johnston

Woollard

et al. 1988

Brit J Clinical Pharma

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“…In the light of recent studies showing an increase in plasma theophylline concentrations in the recumbent position (Warren et al 1985), future studies need to take this into consideration. Finally, adherence to restrictions on intake of xanthine-containing foods and beverages before and during the study should be confirmed by urinary analyses.…”

Section: Mechanisms Of Increase In Plasma Theophylline Concentrationsmentioning

confidence: 98%

Pharmacokinetic Interactions of Cimetidine 1987

Somogyi

Muirhead

1987

Clinical Pharmacokinetics

185

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The number of studies on drug interactions with cimetidine has increased at a rapid rate over the past 5 years, with many of the interactions being solely pharmacokinetic in origin. Very few studies have investigated the clinical relevance of such pharmacokinetic interactions by measuring pharmacodynamic responses or clinical endpoints. Apart from pharmacokinetic studies, invariably conducted in young, healthy subjects, there have been a large number of in vitro and in vivo animal studies, case reports, clinical observations and general reviews on the subject, which is tending to develop an industry of its own accord. Nevertheless, where specific mechanisms have been considered, these have undoubtedly increased our knowledge on the way in which humans eliminate xenobiotics. There is now sufficient information to predict the likelihood of a pharmacokinetic drug-drug interaction with cimetidine and to make specific clinical recommendations. Pharmacokinetic drug interactions with cimetidine occur at the sites of gastrointestinal absorption and elimination including metabolism and excretion. Cimetidine has been found to reduce the plasma concentrations of ketoconazole, indomethacin and chlorpromazine by reducing their absorption. In the case of ketoconazole the interaction was clinically important. Cimetidine does not inhibit conjugation mechanisms including glucuronidation, sulphation and acetylation, or deacetylation or ethanol dehydrogenation. It binds to the haem portion of cytochrome P-450 and is thus an inhibitor of phase I drug metabolism (i.e. hydroxylation, dealkylation). Although generally recognised as a nonspecific inhibitor of this type of metabolism, cimetidine does demonstrate some degree of specificity. To date, theophylline 8-oxidation, tolbutamide hydroxylation, ibuprofen hydroxylation, misonidazole demethylation, carbamazepine epoxidation, mexiletine oxidation and steroid hydroxylation have not been shown to be inhibited by cimetidine in humans but the metabolism of at least 30 other drugs is affected. Recent evidence indicates negligible effects of cimetidine on liver blood flow. Cimetidine reduces the renal clearance of drugs which are organic cations, by competing for active tubular secretion in the proximal tubule of the kidney, reducing the renal clearances of procainamide, ranitidine, triamterene, metformin, flecainide and the active metabolite N-acetylprocainamide. This previously unrecognised form of drug interaction with cimetidine may be clinically important for both parent drug, and metabolites which may be active.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…As shown in Table 2, several studies, for example, with paracetamol [18,20,21], nifedipine [18], amoxycillin [22] and theophylline [23], have found an increase in the time to reach the maximum serum drug concentration (t max )/mean residence time (MRT) and/or a decrease in maximum plasma drug concentration (C max )/ (early) AUC for left lateral and supine position compared to other positions (right lateral, prone, sitting, standing). The effects of the respective postures on pharmacokinetics correspond to their effects on gastric emptying, as discussed above (left lateral and supine positions tend to decrease the rate of gastric emptying).…”

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

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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Posture and theophylline kinetics.

Cited by 43 publications

References 9 publications

Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing.

Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing.

Pharmacokinetic Interactions of Cimetidine 1987

Influence of posture on pharmacokinetics

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