[Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy subjects].
OBJECTIVE
To develop an HPLC-ESI-MS assay for determination of trimebutine in human plasma and to investigate the pharmacokinetics and bioequivalence of two trimebutine tablets in human.


METHODS
After being made alkaline with saturated sodium bicarbonate, plasma was extracted by cyclohexane and separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (pH 3.5)-methanol (18:82). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 388 for trimebutine and m/z 280 for the internal standard (sibutramine, IS). The fragmentor voltage was 50 V. A randomized cross-over design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer.


RESULTS
Calibration curve was linear over the range of 0.3 - 150 microg x L(-1). The main pharmacokinetic parameters of T1/2, Tmax and Cmax were (9.2 +/- 2.8) h, (1.0 +/- 0.3) h and (40 +/- 20) microg x L(-1) for the reference tablet; (9.2 +/- 2.3) h, (0.9 +/- 0.4) h and (41 +/- 20) microg x L(-1) for the test tablet. The relative bioavalability of the test tablet was (97 +/- 13)%. The results of variance analysis and two one-sided t-test showed that there was no significant difference between the two formulations in the AUC and Cmax.


CONCLUSIONS
The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.
Jiang
Hong
H
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
Ding
Li
L
Yang
Jin
J
Huang
Xin
X
Liu
Guang-yu
GY
Zhang
Zheng-xing
ZX
D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets; D013810:Therapeutic Equivalency; D014287:Trimebutine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D005765:Gastrointestinal Agents; D013607:Tablets; D014287:Trimebutine