Pharmacokinetics of tolmetin with and without concomitant administration of antacid in man
Autor: | E. F. Lemanowicz, M. R. Hallmark, E. Sakmar, J. W. Ayres, J. MacKichan, John G. Wagner, Donald J. Weidler |
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Rok vydání: | 1977 |
Předmět: |
Adult
Male Time Factors Sodium Metabolite medicine.medical_treatment chemistry.chemical_element Urine Pharmacology chemistry.chemical_compound Pharmacokinetics Antacid medicine Humans Pharmacology (medical) Drug Interactions Pyrroles Tolmetin General Medicine Bioavailability Kinetics chemistry Concomitant Antacids medicine.drug |
Zdroj: | European journal of clinical pharmacology. 12(6) |
ISSN: | 0031-6970 |
Popis: | The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0-∞ for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides. |
Databáze: | OpenAIRE |
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