Bioequivalence and pharmacokinetic comparison of two mycophenolate mofetil formulations in healthy Chinese male volunteers: An open-label, randomized-sequence, single-dose, two-way crossover study

Zhang, Qian; Tao, Yifu; Zhu, Yubing; Zhu, Dingchun

doi:10.1016/j.clinthera.2010.01.013

Cited by 13 publications

(15 citation statements)

References 12 publications

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“…Several methods have been reported for the analysis of MPA and its metabolites in different biological fluids by electrophoresis [11] , [12] , [13] , [14] , immunoassay technique [15] , [16] , [17] , high performance liquid chromatography using diode array [18] , fluorescence [19] , [20] , [21] , UV [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , and mass spectrometry detection [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] . Relatively few UPLC–MS/MS based methods are available in literature for rapid analysis of MPA in biological samples [42] , [43] .…”

Section: Introductionmentioning

confidence: 99%

Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry

Upadhyay

Trivedi

Shah

et al. 2014

Journal of Pharmaceutical Analysis

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A simple, sensitive and high throughput ultra performance liquid chromatography tandem mass spectrometry method has been developed for the determination of mycophenolic acid in human plasma. The method involved simple protein precipitation of MPA along with its deuterated analog as an internal standard (IS) from 50 µL of human plasma. The chromatographic analysis was done on Acquity UPLC C18 (100 mm×2.1 mm, 1.7 µm) column under isocratic conditions using acetonitrile and 10 mM ammonium formate, pH 3.00 (75:25, v/v) as the mobile phase. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for quantitation. In-source conversion of mycophenolic glucuronide metabolite to the parent drug was selectively controlled by suitable optimization of cone voltage, cone gas flow and desolvation temperature. The method was validated over a wide concentration range of 15–15000 ng/mL. The mean extraction recovery for the analyte and IS was >95%. Matrix effect expressed as matrix factors ranged from 0.97 to 1.02. The method was successfully applied to support a bioequivalence study of 500 mg mycophenolate mofetil tablet in 72 healthy subjects.

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Section: Introductionmentioning

confidence: 99%

Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry

Upadhyay

Trivedi

Shah

et al. 2014

Journal of Pharmaceutical Analysis

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“…It then appears that mycophenolate mofetil dissolution needs only to be assayed at a pH of 1.2, as established in the FDA recommendations . In vitro dissolution data at higher pH values are irrelevant to in vivo bioavailability, as demonstrated by the fact that several mycophenolate mofetil generics are bioequivalent to the innovator product in adult healthy volunteers , despite variations in dissolution at higher pH values . The interaction with proton pump inhibitors may have relevance, as they increase the gastric pH and slow the hydrolization of mycophenolate mofetil resulting in a reduction of maximum exposure and availability .…”

Section: Discussionmentioning

confidence: 99%

“…Hence, low bioavailability cannot be attributed to patients not taking the drug, but to patient conditions. Previous studies have documented that certain pediatric patients exhibit very low mycophenolic acid exposure after mycophenolate mofetil administration, although the exact reasons for poor bioavailability in certain individuals have not yet been elucidated . Such patients require higher mycophenolate doses.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, drug dissolution in the gastrointestinal tract is a rate‐controlling step for absorption . Mycophenolate mofetil generics are available in different countries, and studies documenting the bioequivalence of several of these products with the innovator CellCept ® have been published . Bioequivalence testing considers only bioavailability data resulting from circulating drug concentrations determined in adult healthy volunteers .…”

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confidence: 99%

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Bioavailability of a generic of the immunosuppressive agent mycophenolate mofetil in pediatric patients

González-Ramírez

González-Bañuelos

Villa

et al. 2014

Pediatric Transplantation

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The use of generic immunosuppressive agents is controversial, especially for the treatment of pediatric patients, as information on the bioavailability of generic immunosuppressants in children is particularly scarce. The aim of the study was to compare the bioavailabilities of two products containing mycophenolate mofetil, the innovator and a generic, in children. Pediatric patients with end-stage renal disease on the waiting list for renal transplantation received a single oral dose of mycophenolate mofetil as either the innovator product (CellCept(®) , Roche) or the generic (Tevacept(®) , Teva Pharmaceuticals). A nine point pharmacokinetic profile was obtained. Mycophenolic acid concentration was quantitated in plasma by HPLC, plasma concentration-against-time curves were constructed, and bioavailability parameters were determined. Pharmaceutical quality analysis of both formulations, including drug content and dissolution profile, was also performed. There were no statistically significant differences between formulations in bioavailability parameters. Interindividual variability was very important, but individual values of AUC, an indicator of the extent of drug absorption, were within the same range for both formulations. The two formulations exhibited similar drug content and dissolution profiles, as well as comparable mycophenolic acid plasma levels in an end-stage renal failure population.

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“…La farmacocinética del MPA ha sido extensamente estudiada en voluntarios sanos y en pacientes trasplantados. Un análisis exhaustivo de la literatura refl eja una amplia variabilidad en los parámetros farmacocinéticos del fármaco, atendiendo a las dosis utilizadas, tiempos de muestreo y condición clínica de los pacientes [4][5][6][7][8] . MMF es absorbido de forma rápida y es ampliamente metabolizado presistémicamente a MPA 8 .…”

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Estudio de biodisponibilidad relativa entre dos formulaciones orales de micofenolato mofetilo en voluntarios sanos

et al. 2011

Rev. méd. Chile

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Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers Background: The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. Aim: To evaluate the relative bioavailability for an oral formulation of mycophenolate mofetil (MMF) (Linfonex TM) compared to the reference formulation (Cellcept TM) to determine the bioequivalence between both formulations. Material and Methods: A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chromatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and area under plasma concentration curve versus time after administration between 0 and infi nity, were calculated for both products. Results: The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically signifi cant differences were found in calculated pharmacokinetic parameters between both formulations. Conclusions: Linfonex TM 500 mg is bioequivalent to Cellcept TM 500 mg.

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Bioequivalence and pharmacokinetic comparison of two mycophenolate mofetil formulations in healthy Chinese male volunteers: An open-label, randomized-sequence, single-dose, two-way crossover study

Cited by 13 publications

References 12 publications

Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry

Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry

Bioavailability of a generic of the immunosuppressive agent mycophenolate mofetil in pediatric patients

Estudio de biodisponibilidad relativa entre dos formulaciones orales de micofenolato mofetilo en voluntarios sanos

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