Pharmacokinetics and bioequivalence of two trimebutine formulations in healthy volunteers using desmethyl-trimebutine levels.
Trimebutine tablets (dimethylamino-2-phenyl-2-n-butyl-3,4,5- trimethoxybenzoate maleate, CAS 34140-59-5, reference) and a new tablet formulation (Eurogalena, test) were administered in 24 healthy volunteers of both sexes according to a cross-over design, in a single dose of one 100 mg tablet of each formulation. Blood samples were drawn off over a 24-h period, before (time 0) and after each administration at specific intervals. Trimebutine and its main active metabolite, desmethyl-trimebutine, were measured in plasma using a validated HPLC method with UV detection. For both compounds, the sensitivity was 20 ng.ml-1 and the analytical method was proved to be linear for concentrations between 20 ng.ml-1 and 5000 ng.ml-1, with a variability less than 11%. The non-compartmental method was used for pharmacokinetic analysis. The confidence interval approach was used for comparison of the formulations according to the EU guidance note on bioavailability and bioequivalence on Cmax, AUC0-t and AUC0-infinity, log transformed. Tmax values were statistically compared using the Friedman non-parametric test. No trimebutine concentration was measured in the plasma samples. The obtained data with desmethyl-trimebutine proved the bioequivalence of the two tested formulations.
Saivin
S
S
Laboratoire de Pharmacocinétique et de Toxicologie Clinique, Centre Hospitalier Universitaire de Toulouse, France.
Lavit
M
M
Michel
F
F
Labaune
J P
JP
Martin
A
A
Cahiez
G
G
Donazzolo
C
C
Chomard
J M
JM
Houin
G
G
D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D013810:Therapeutic Equivalency; D014287:Trimebutine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
D005765:Gastrointestinal Agents; D013607:Tablets; C053065:N-desmethyltrimebutine; D014287:Trimebutine