RESUMEN
OBJECTIVE: In this study a bioanalytical method for digoxin quantification was developed using Abbott AxSYM Digoxin II with fluorescence detection to assess the bioequivalence of two digoxin tablet formulations (Digox 0.25 mg tablet from Pharlab Ind. Ltd., Brazil as test formulation and Digoxin 0.25 mg tablet from Laboratório Glaxo SmithKline, Brazil as reference formulation). MATERIAL AND METHODS: 30 healthy volunteers (both sexes) received a single oral dose of digoxin in an open, randomized, two-period crossover study with a seven half-life washout interval of at least (21 days). Plasma samples were obtained over a 288-h interval after each oral administration of digoxin. The present method utilizes microenzyme particle immunoassay technology, in which the digoxin in the sample binds to anti-digoxin-coated microparticles and after separation; digoxin-alkaline phosphatase conjugate binds to the available sites remaining. Digoxin concentrations are calculated from the fluorescent products generated as a result of substrate (4-methylumbelliferyl) passage through the matrix cell. RESULTS: The method was shown to be specific and sensitive with good accuracy and precision. The geometric mean and 90% confidence intervals (CI) for the Digox/Digoxin ratio were 107.62% (96.71 - 119.80%) for AUC0-t, 97.15% (80.54 - 117.19%) for AUC0-inf, and 91.23% (83.55 - 99.62%) for Cmax. CONCLUSION: Since the 90% CI for the parameters were all within the 80 - 125% interval proposed by the US Food and Drug Administration Agency, the two formulations were considered bioequivalent in terms of rate and extent of absorption.
Asunto(s)
Cardiotónicos/sangre , Cardiotónicos/farmacocinética , Digoxina/sangre , Digoxina/farmacocinética , Técnicas para Inmunoenzimas/métodos , Adolescente , Adulto , Área Bajo la Curva , Cardiotónicos/administración & dosificación , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Digoxina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Comprimidos , Equivalencia TerapéuticaRESUMEN
OBJECTIVE: In this study, the bioavailability of 2 meloxicam 15 mg tablet formulations was compared. A single dose of each formulation was administered to 24 healthy volunteers (12 males and 12 females). MATERIAL AND METHODS: The study was conducted using an open, randomized and crossover design with a 2-week washout interval. The plasma samples were obtained over a 96-hour interval and meloxicam concentrations were analyzed by high-performance liquid chromatography (an agilent) coupled to an API 2000 turboionspray tandem mass spectrometry (LC-MS-MS). An electrospray ionization (ESI) source operating in the positive ion mode, using a cross flow counter electrode and set for the multiple reaction monitoring (MRM) was employed. The plasma protein precipitate was reconstituted with acetonitrile/water + 10 mM acetic acid (20/80, v/v) and injected in a Prevail C8 5 microm (150 mm x 4.6 mm i.d.) analytical column with reverse-phase liquid chromatography. The retention time observed for meloxicam and tenoxicam (internal standard) was 1.8 and 1.4 minutes, respectively. The mean recovery of meloxicam was 95.9% and the limit ofquantification was 0.02 microg/ml. RESULTS: The geometric mean of meloxicam/movatec 15 mg individual % ratio was 101.3% for AUC(last), 99.9% for AUC(0-infinity) and 107.7% for C(max). The 90% confidence intervals were 97.3 - 105.4%, 96.0 - 104.0% and 98.8 - 117.4%, respectively. CONCLUSION: Since the 90% CI for both AUC(Iast), AUC(0-infinity) and C(max), ratios were all inside the 80 - 125% interval proposed by the US Food and Drug Administration Agency and accepted by Brazilian ANVISA (Sanitary Surveillance Agency), it was concluded that the meloxicam formulation produced by Merck S.A. lndústrias Químicas is bioequivalent to the movatec formulation regarding both the rate and extent of absorption. This assay method was faster, more simple, specific, precise and accurate in determining the bioequivalence of meloxicam than any method previously described.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Inhibidores de la Ciclooxigenasa/farmacocinética , Espectrometría de Masas en Tándem/métodos , Tiazinas/farmacocinética , Tiazoles/farmacocinética , Adulto , Área Bajo la Curva , Brasil , Estudios Cruzados , Inhibidores de la Ciclooxigenasa/sangre , Femenino , Semivida , Humanos , Masculino , Meloxicam , Valores de Referencia , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/métodos , Equivalencia Terapéutica , Tiazinas/sangre , Tiazoles/sangreRESUMEN
OBJECTIVE: To assess the bioequivalence of a ramipril 5 mg tablet formulation (ramipril test formulation from Laboratórios Biosintética Ltda (Sao Paulo, Brazil) and Triatec from Aventis Pharma (Sueano, Brazil) standard reference formulation) in 26 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, 2-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 36-hour period. Plasma ramipril and ramiprilat concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the ramipril and ramiprilat plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUClast, AUCinf and Cmax. RESULTS: The limit of quantification was 0.2 ng x ml(-1) and 1.0 ng x ml(-1) for ramipril and ramiprilat, respectively. The geometric means and 90% confidence intervals (CI) for Ramipril/Triatec and Ramiprilat/Triatec percent ratios were: 104.69% (90% CI = 93.21-117.59%) for Cmax, 102.49% (90% CI = 92.76-113.24%) for AUClast, 103.60% (90% CI = 93.56 114.73%) for AUCinf, 108.48% (90% CI = 98.86-119.03%) for Cmax, 105.88% (90% CI = 101.55-110.39%) for AUClast, 97.30% (90% CI = 90.17-104.99%) for AUCinf, respectively. CONCLUSION: Since the 90% CI for AUClast, AUCinf and Cmax ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that the ramipril formulation produced by Laboratórios Biosintética Ltda is bioequivalent to the Triatec formulation in both rate and extent of absorption.
Asunto(s)
Antihipertensivos/farmacocinética , Ramipril/farmacocinética , Administración Oral , Adolescente , Adulto , Antihipertensivos/administración & dosificación , Antihipertensivos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica/métodos , Cromatografía Liquida/métodos , Estudios Cruzados , Femenino , Humanos , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Ramipril/administración & dosificación , Ramipril/análogos & derivados , Ramipril/sangre , Valores de Referencia , Espectrometría de Masa por Ionización de Electrospray/métodos , Equivalencia Terapéutica , Factores de TiempoRESUMEN
OBJECTIVE: To compare the bioavailability of two potassic losartan immediate release tablet (50 mg) formulations (Losartan from Laboratórios Cristália Ltd., Brazil, as a test formulation and Cozaar from Merck Sharp & Dohme Farmacêutica Ltd., Brazil, as a reference formulation) in 25 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted in an open, randomized, 2-period crossover design and a 1-week washout period. Plasma samples were obtained over a 24-hour interval. The concentrations of losartan and its active metabolite losartan acid were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using a selected ion monitoring method. From the losartan and losartan acid plasma concentrations vs. time curves the following pharmacokinetic parameters were obtained: AUClast, AUC0-inf and Cmax. RESULTS: The geometric mean and respective 90% confidence interval (CI) of Losartan/Cozaar losartan percent ratios were 92.9% (82.2-105.0%) for Cmax, 99.0% (92.5-105.9%) for AUClast, and 99.1% (92.7-105.8%) for AUC0-inf. Furthermore, the geometric mean and respective 90% CI of Losartan/Cozaar losartan acid percent ratios were 98.5% (91.5-106.0%) for Cmax, 97.9% (93.3 102.7%) for AUClast, and 98.1% (93.6-102.9%) for AUC0-inf. CONCLUSION: Since the 90% CI for Cmax, AUClast and AUC0-inf were within the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that the potassic losartan immediate release 50 mg tablet was bioequivalent to the Cozaar immediate release 50 mg tablet, according to both the rate and extent of absorption. While there were no significant differences in the bioequivalence assessed by either losartan or losartan acid, future bioequivalence studies on losartan may be performed by quantifying losartan alone as the parent compounds are more discriminative.
Asunto(s)
Antihipertensivos/farmacocinética , Losartán/farmacocinética , Adulto , Antihipertensivos/sangre , Área Bajo la Curva , Disponibilidad Biológica , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Femenino , Semivida , Humanos , Losartán/sangre , Masculino , Espectrometría de Masas , Equivalencia TerapéuticaRESUMEN
OBJECTIVE: The aim of this study was to compare the bioavailability of two citalopram formulations (citalopram from Eurofarma Laboratórios Ltda., as the test formulation, and cipramil from Schering-Plough, Brazil, as the reference formulation) in healthy volunteers. METHODS: The study had an open, randomized, two-period crossover design with a two-week washout interval between doses. The samples were obtained over a 168-hour interval after each oral administration of citalopram (one 20 mg tablet of each formulation). The analyte and the internal standard were extracted from plasma using diethylether: dichloromethane (70 : 30, v/v) and the extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Chromatography was done isocratically using a Genesis C8 analytical column (4 microm, 2.1 mm i.d. x 100 mm). The method had a chromatographic run time of three minutes and a linear calibration curve over the range of 0.5 - 200 ng x ml(-1) (r2 > 0.999887). The limit of quantification was 0.5 ng x ml(-1). RESULTS: The geometric mean and 90% confidence intervals (CI) for the citalopram/cipramil ratio were 98.28% (94.24 - 102.49%) for AUClast, 96.44% (90.20 - 103.11%) for AUCinf, and 98.54% (94.70 - 102.54%) for Cmax. CONCLUSION: Since the 90% CI for Cmax, AUClast and AUC(0-infinity) ratios were all within the 80 - 125% interval proposed by the US Food and Drug Administration, we concluded that the citalopram formulation elaborated by Eurofarma Laboratórios Ltda. was bioequivalent to the cipramil formulation in its rate and extent of absorption.