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

Abstract

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.

Number‐dependent association of potentially inappropriate medications with clinical outcomes and expenditures among community‐dwelling older adults: A population‐based cohort study

“…This time interval was chosen considering that 14 days would cover a minimum of four to six half‐lives of the medications on the Beers Criteria (allowing drugs to reach steady states with constant dosing). The interval allowed an adequate evaluation of the association between PIM prescribing and clinical outcomes 21–27 . Patients were followed up after an initial prescription fill until the date of hospitalizations or ED visits or upon the study's conclusion (30 September 2016).…”

“…The interval allowed an adequate evaluation of the association between PIM prescribing and clinical outcomes. [21][22][23][24][25][26][27] Patients were followed up after an initial prescription fill until the date of hospitalizations or ED visits or upon the study's conclusion (30 September 2016).…”

A Comparison of the Effect of Timegadine, Levamisole, and D‐Penicillamine on Human Neutrophil Metabolism of Endogenous Arachidonic Acid and Chemotaxis

“…( 2.4-9.7) (3.7-9.9) (3.6-9.4) (4.3-9.7) (3.8-9.4) volunteers, 250 mg b.i.d., results in maximal serum concentrations of 1.71 k0.16 pg/ml, equal to (4.26k0.40) x M, under steady state conditions (George et al 1986). As seen in fig.…”