ArticleBritish journal of clinical pharmacology2003
Influence of age on the enantiomeric disposition of ibuprofen in healthy volunteers.
Article in British journal of clinical pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- Comparison of intranasal ketorolac tromethamine pharmacokinetics in younger and older adults.Drugs & aging · 2012Trial
- Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability.Clinical pharmacokinetics · 2021Review
- Article
- Ibuprofen-Loaded Hyaluronic Acid Nanofibrous Membranes for Prevention of Postoperative Tendon Adhesion through Reduction of Inflammation.International journal of molecular sciences · 2019Article
- Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model.Frontiers in pharmacology · 2019Article
- Article
- Influence of Sex and Food on the Bioavailability and the R-to-S Conversion of Ketoprofen Stereoisomers in Humans.European journal of drug metabolism and pharmacokinetics · 2017Article
- Stereoselective Conversion of Ketoprofen in Men Versus Women from Two Different Oral Dosage Formulations: Observations and Introspection of the Pharmacokinetic Data.European journal of drug metabolism and pharmacokinetics · 2017Article
- Free drug metabolic clearance in elderly people.Clinical pharmacokinetics · 2008Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo determine the influence of age on the enantioselective disposition of ibuprofen in humans.
methodsHealthy young (n = 16; aged 20-36 years) and elderly (n = 16; aged 66-84 years) volunteers were given a 400-mg oral dose of racemic ibuprofen, and blood and urine samples were collected for 24 h post drug administration. Serum concentrations, total and free, and urinary excretion of both enantiomers of ibuprofen together with the urinary excretion of the stereoisomers of the two major metabolites of the drug, both free and conjugated, were determined by high-performance liquid chromatography.
resultsAgeing had little effect on the distribution and metabolism of R-ibuprofen, unbound clearance of the R-enantiomer via inversion being approximately two-fold that via noninversion mechanisms in both age groups. In contrast, the free fraction of S-ibuprofen was significantly greater [33%; young 0.48 +/- 0.10%; elderly 0.64 +/- 0.20%] mean difference -0.16; 95% confidence interval (CI) -0.05, -0.27; P < 0.01; and the unbound clearance of the drug enantiomer was significantly lower (28%; young 15.9 +/- 2.2 l min-1; elderly 11.5 +/- 4.1 l min-1; mean difference 4.4; 95% CI 2.12, 6.68; P < 0.001) in the elderly. The metabolite formation clearances of S-ibuprofen via glucuronidation, and oxidation at the 2- and 3- positions of the isobutyl side chain decreased by 24, 28 and 30%, respectively, in the elderly compared with the young, the differences between the two age groups being significant in each case (P < 0.05).
conclusionsFollowing administration of racemic ibuprofen age-associated stereoselective alterations in drug disposition have been observed, with the elderly having increased free concentrations and lower unbound clearance of the S-enantiomer in comparison with the young. In contrast, the handling of the R-enantiomer is essentially unaltered with age. The results of this study indicate that the elderly have an increased exposure to the active ibuprofen enantiomer and thus some caution may be required when using this drug in this age group.
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