RESUMO
In the present study, a novel, fast, sensitive and robust method to quantify budesonide in human plasma using 3-keto-desogestrel as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by liquid-liquid extraction (LLE) using ether. Extracted samples were analyzed by high performance liquid chromatography coupled to Atmospheric pressure photoionization tandem mass spectrometry (HPLC-APPI-MS/MS). Chromatography was performed isocratically on a C18, 5 µm analytical column. The temperature of the autosampler was kept at 6 °C and the run time was 4.00 min. A linear calibration curve over the range 7.5-1000 pg ml⻹ was obtained and the lowest concentration quantified was 7.5 pg ml⻹, demonstrating acceptable accuracy and precision. This analytical method was applied in a relative bioavailability study in order to compare a test budesonide 64 µg/dose nasal spray formulation vs. a reference 64 µg/dose nasal spray formulation (Budecort Aqua) in 48 volunteers of both sexes. The study was conducted in an open randomized two-period crossover design and with a one-week washout period. Plasma samples were obtained over a 14 h interval. Since the 90% CI for both C(max), AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration and ANVISA, it was concluded that budesonide 64 µg/dose nasal spray was bioequivalent to Budecort Acqua® 64 µg/dose nasal spray, according to both the rate and extent of absorption.
Assuntos
Budesonida/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Disponibilidade Biológica , Broncodilatadores/administração & dosagem , Broncodilatadores/sangue , Broncodilatadores/farmacocinética , Budesonida/administração & dosagem , Budesonida/sangue , Estudos Cross-Over , Desogestrel/sangue , Estabilidade de Medicamentos , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Equivalência TerapêuticaRESUMO
OBJECTIVE: To investigate growth and markers of collagen and bone metabolism in prepubertal children with asthma. STUDY DESIGN: We measured growth velocity over 12 months and markers of collagen types I and III synthesis (PINP, PICP, PIIINP), collagen type I degradation (ICTP), and bone metabolism (bone-specific alkaline phosphatase and osteocalcin) on one occasion in 56 prepubertal children with stable asthma, 39 of whom were treated with inhaled budesonide or beclomethasone. Collagen data were compared with normal control values. RESULTS: Children treated with inhaled steroids had reduced collagen synthesis (PINP, PIIINP) compared with control subjects (p = 0.038, p = 0.045), although PICP was increased (p = 0.05). Carboxyterminal telopeptide of type I collagen was reduced in patients treated with inhaled steroids (p < 0.0005) compared with nonsteroid-treated patients. Serum osteocalcin but not bone-specific alkaline phosphatase was significantly reduced in children treated with inhaled steroids (p < 0.02). Significant correlation was observed between PIIINP and ICTP and growth velocity. CONCLUSION: Collagen turnover is reduced in children with asthma receiving long-term inhaled steroid treatment. Markers of collagen synthesis provide a more accurate reflection of growth disturbance than osteocalcin and bone-specific alkaline phosphatase.