The influence of food intake on the bioavailability of timegadine, a novel non‐steroidal anti‐inflammatory drug.

George, S; Dauwe, K; McBurney, A; Ward, John W.

doi:10.1111/j.1365-2125.1983.tb01537.x

Cited by 6 publications

(3 citation statements)

References 14 publications

(18 reference statements)

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“…Six potentially relevant studies identified in http://clinicaltrials.gov did not provide any results and could not be used (Supplementary Table ). We included 38 publications with 656 unique individuals, reporting 46 fed/fasted comparisons involving 874 participants in the comparisons. Papers were published between 1972 and 2012.…”

Section: Resultsmentioning

confidence: 99%

Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review

Moore

Derry

Wiffen

et al. 2015

Brit J Clinical Pharma

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AimsIt is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse effects. The efficacy of single dose analgesics depends on producing high, early, plasma concentrations; food may interfere with this. This review sought evidence from single dose pharmacokinetic studies on the extent and timing of peak plasma concentrations of analgesic drugs in the fed and fasting states.MethodsA systematic review of comparisons of oral analgesics in fed and fasting states published to October 2014 reporting kinetic parameters of bioavailability, time to maximum plasma concentration (tmax), and its extent (Cmax) was conducted. Delayed-release formulations were not included.ResultsBioavailability was not different between fasted and fed states. Food typically delayed absorption for all drugs where the fasting tmax was less than 4 h. For the common analgesics (aspirin, diclofenac, ibuprofen, paracetamol) fed tmax was 1.30 to 2.80 times longer than fasted tmax. Cmax was typically reduced, with greater reduction seen with more rapid absorption (fed Cmax only 44–85% of the fasted Cmax for aspirin, diclofenac, ibuprofen and paracetamol).ConclusionThere is evidence that high, early plasma concentrations produces better early pain relief, better overall pain relief, longer lasting pain relief and lower rates of remedication. Taking analgesics with food may make them less effective, resulting in greater population exposure. It may be time to rethink research priorities and advice to professionals, patients and the public.

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Section: Resultsmentioning

confidence: 99%

Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review

Moore

Derry

Wiffen

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…The purified proteins: HSA, AGP, AAT (George et al, 1983), and multiple dose work in progress, gave plasma concentrations between 0.05 and 2.32 ,ug/ml (mean 0.81 ,ug/ml), therefore 1.0 ,ug/ml was used for all binding work (except concentration effects). The dialysis buffer was Sorensen's phosphate buffer pH 7.4 made by mixing 800 ml of Na2HPO4 (9.46 g/l) with 200 ml of KH2PO4 (9.07 g/l) and adjusting the pH using one or other of the salt solutions.…”

Section: Purified Proteinsmentioning

confidence: 99%

“…Previous work with single doses of timegadine administered to healthy volunteers (George et al, 1983) suggested a T½, of 3.2 + 0.3 h (mean + s.e. mean), but multiple dose work in progress to study the steady state pharmacokinetics of timegadine suggest a T½, of 6.6 ± 1.1 h (mean + s.e.…”

Section: Introductionmentioning

confidence: 99%

The protein binding of timegadine determined by equilibrium dialysis.

George¹,

McBurney²,

Ward³

1984

Brit J Clinical Pharma

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The protein binding of timegadine to albumin, serum, plasma and plasma enriched with the acute phase reactants alpha 1‐acid glycoprotein, alpha 1‐anti‐trypsin and C‐reactive protein was determined by equilibrium dialysis. The effects of other analgesic and anti‐ inflammatories (indomethacin, ketoprofen, paracetamol and sodium salicylate) and other basic drugs (disopyramide, lignocaine, propranolol and quinidine) on the binding of timegadine were also determined. Timegadine binding was concentration‐dependent up to 0.5 micrograms/ml, but independent above this level up to 10.0 micrograms/ml, the mean and standard error being 93.8 +/‐ 0.5%. Albumin accounted for only 32.4% of timegadine bound to plasma. Plasma enrichment with the acute phase reactants led to significant increases in timegadine binding. Simultaneous dialysis with other drugs caused significant decreases in timegadine binding.

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The pharmacokinetics of timegadine and two of its metabolites after multiple oral dosing, and the effects of concomitant administration of ibuprofen

George

McBurney

Ward

1986

Eur J Clin Pharmacol

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A 250 mg tablet of timegadine was given twice daily for 15 days to 13 healthy volunteers. On Day 16 a single morning dose of timegadine was supplemented by two 200 mg tablets of a proprietary brand of ibuprofen. Serum concentrations of timegadine were measured by high pressure liquid chromatography, and steady state was achieved between Days 5 and 8. Serum concentrations of two metabolites of timegadine, MI and MII were measured by thin layer chromatography by Leo Pharmaceutical Products, Denmark. Ibuprofen did not significantly affect the serum half-time of timegadine, but did reduce the maximum measured serum timegadine concentration, the area under the serum concentration versus time curve and the time to achieve maximum measured serum concentration. Serum liver enzymes remained within the normal ranges and there were no changes in hepatic microsomal enzyme activity as assessed by urinary excretion of D-glucaric acid.

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The influence of food intake on the bioavailability of timegadine, a novel non‐steroidal anti‐inflammatory drug.

Cited by 6 publications

References 14 publications

Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review

Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review

The protein binding of timegadine determined by equilibrium dialysis.

The pharmacokinetics of timegadine and two of its metabolites after multiple oral dosing, and the effects of concomitant administration of ibuprofen

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