RESUMO
Aim To evaluate the pharmacokinetics and bioequivalence of two osmotic pump tablets of hydrochloride venlafaxine in Chinese healthy volunteers.Methods The fed test each enrolled twenty-six Chinese healthy volunteers in a randomized-sequence, open-label, two-period crossover single-dose oral test and reference preparations of hydrochloride venlafaxine extended-release tablets.The plasma concentrations of venlafaxine and its active metabolites O-desmethylvenlafaxine were determined by a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method, and the pharmacokinetic parameters and bioequivalence of the two tablets were analyzed using PhoenixTM WinNonlin 6.4 software.Results The pharmacokinetic parameters of venlafaxine after single dose for the test and reference tablets were as follows: Cmax(58.50±19.47)vs(60.14±22.18)μg•L-1, AUC0-t(1 074.1±526.7)vs(1 057.9±539.7)μg•h•L-1, AUC0-∞(1 084.7±536.8)vs(1 067.8±554.0)μ g•h•L-1.The pharmacokinetic parameters of O-desmethylvenlafaxine were as follows: Cmax(101.63±29.64)vs(101.45±31.62)μg•L-1, AUC0-t(2 694.0±834.5)vs(2 702.9±946.4)μg• h•L-1, AUC0-∞(2 753.9±885.5)vs(2 753.2±988.4)μg•h•L-1.The 90% confidence intervals of the geometric mean ratios of Cmax, AUC0-t, AUC0-∞ for the test preparation and the reference preparationwere all within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference preparations of hydrochloride venlafaxine extended-release tablets are bioequivalent in Chinese healthy volunteers under fed conditions.
RESUMO
OBJECTIVE: To establish a liquid chromatography tandem mass spectrometry (LC-MS-MS) method for simultaneous determination of venlafaxine (Ven) and its active metabolite, O-desmethylvenlafaxine (ODV), in human plasma, and to investigate the pharmacokinetics and bioequivalence of Ven and ODV in venlafaxine hydrochloride capsules in Chinese healthy volunteers. METHODS: Twenty-two volunteers took a single oral dose (50 mg) of venlafaxine hydrochloride capsules by 2-way crossover design. The concentrations of Ven and ODV in plasma were determined by HPLC-MS-MS. The pharmacokinetic parameters were calculated by BAPP software. RESULTS: Blood samples were deproteinized . The calibration curves of Ven and ODV were linear in the range from 1.99 to 510 μg · L-1 (r=0.9997) and 1.96 to 501 μg · L-1 (r=0.9999), respectively. The relative recovery was 92.2%-105.9%. The intra-day and inter-day RSDs were less than 10.5%. The pharmacokinetic parameters of test and reference capsules of Ven were as follows: ρmax were (68.90 ± 23.8) and (69.81 ± 23.73) μg · L-1, tmax were (2.2 ± 0.7) and (1.9 ± 0.8) h, t1/2 were (5.0 ± 1.1) and (4.9 ± 1.6) h, AUC0-24 were (547.91 ± 288.66) and (592.70 ± 330.70) μg · h · L-1, respectively; the pharmacokinetic parameters of test and reference capsules of ODV were as follows; ρmax were (73.88 ± 21.18) and (73.96 ± 22.09) μg · L-1, tmax were (3.8 ± 1.8) and (4.0 ± 1.6) h, t1/2 were (8.7 ± 1.8) and (8.9 ± 1.9) h, AUC0-48 were (1 224.41 ± 239.46) and (1243.53 ± 287.19) μg · h · L-1, respectively. The relative bioavalabilities of Ven and ODV in the test capsules were (107.8 ± 22.0)% and (99.6 ± 10.7)%, respectively. CONCLUSION: The HPLC-MS-MS method for simultaneous determination of Ven and ODV in plasma is proved to be sensitive, accurate and convenient. The reference and test capsules are bioequivalent. Copyright 2012 by the Chinese Pharmaceutical Association.