Variability in the Disposition of Ibuprofen Enantiomers in Osteoarthritis Patients
| Autor: | Qian Xiaotao, Anita C. Rudy, Stephen D. Hall, Sarah I. Ryan, Lorrie A. Kalasinski, John D. Bradley |
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| Rok vydání: | 1992 |
| Předmět: |
Adult
Male Knee Joint Metabolite Ibuprofen Urine Pharmacology Drug Administration Schedule Osteoarthritis Hip chemistry.chemical_compound Double-Blind Method Pharmacokinetics Oral administration Osteoarthritis Humans Medicine Tissue Distribution Pharmacology (medical) Dosing Aged Aged 80 and over Dose-Response Relationship Drug business.industry organic chemicals Area under the curve Stereoisomerism Middle Aged chemistry Female Enantiomer business medicine.drug |
| Zdroj: | Therapeutic Drug Monitoring. 14:464-470 |
| ISSN: | 0163-4356 |
| DOI: | 10.1097/00007691-199212000-00005 |
| Popis: | The pharmacokinetics of the enantiomers of ibuprofen have been investigated following oral administration of 300 or 600 mg of racemic ibuprofen four times daily to 45 patients with osteoarthritis. Fifteen of these patients also received single doses of 300 or 600 mg of racemic ibuprofen. Serum concentrations of R- and S-ibuprofen and urine concentrations of the stereoisomers of ibuprofen and its metabolites were measured by high-performance liquid chromatography. The fraction inverted (F(inv)) of the inactive R- to active S-ibuprofen was estimated by a urinary metabolite method. For the 15 patients in both the chronic and single dose studies, there were no significant differences in the clearance of R-ibuprofen or F(inv). The elimination half-lives of R- and S-ibuprofen were comparable for the single and chronic dosing studies. The area under the curve (AUC) values, 6-h trough concentrations, and average steady state concentrations of the R- and S-enantiomers were statistically different after chronic dosing. Despite considerable variability in the clearances in these patients, e.g., clearance (CL) of R-ibuprofen showed 28-49% CV, much less variability was seen in F(inv) (range 9-19% CV), implying that patients would receive similar effective doses of active S-ibuprofen in spite of large differences in kinetics. |
| Databáze: | OpenAIRE |
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