RESUMO
BACKGROUND AND OBJECTIVE: Lung biopsies from patients with hypersensitivity pneumonitis (HP) have demonstrated small airway (SA) involvement, but there is no information concerning SA function in HP, and it is unknown whether pharmacological treatment could modify its function. SA function in patients with chronic HP using ultrasonic pneumography (UPG) and impulse oscillometry (IOS) was explored. We also compared initial results with those obtained after 4 weeks of standardized treatment with azathioprine and prednisone. METHODS: The study group consisted of adults with recent diagnoses of HP. All patients completed UPG, IOS, spirometry, body plethysmography, single-breath carbon monoxide diffusing capacity (DLCO ) and the 6-min walk test (6MWT). The fraction of exhaled nitric oxide (FENO ) was obtained to assess eosinophilic airway inflammation. Measurements were taken at diagnosis and after 4 weeks of treatment. RESULTS: A total of 20 consecutive patients (16 women) with chronic HP participated in the study. Median age was 50 years (interquartile range (IQR): 42-54). At diagnosis, the UPG phase 3 slope was abnormally high, consistent with maldistribution of ventilation. For IOS, all patients had low reactance at 5 Hz (X5) and elevated reactance area (AX) reflecting low compliance, and only eight (40%) patients had elevated R5 (resistance at 5 Hz (total)) and R5-20 (resistance at 5 Hz-resistance at 20 Hz (peripheral)) attributed to SA resistance. In contrast, FENO parameters were within normal limits. After treatment, forced vital capacity (FVC), the 6-min walk distance and the distribution of ventilation showed significant improvement, although DLCO did not. CONCLUSION: Patients with chronic HP have SA abnormalities that are partially revealed by the UPG and IOS tests. Lung volumes, but not gas exchange, improved after treatment with azathioprine and prednisone.
Assuntos
Alveolite Alérgica Extrínseca , Azatioprina/farmacocinética , Pulmão , Prednisolona/farmacocinética , Resistência das Vias Respiratórias/fisiologia , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/tratamento farmacológico , Alveolite Alérgica Extrínseca/fisiopatologia , Anti-Inflamatórios/farmacocinética , Disponibilidade Biológica , Testes Respiratórios/métodos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oscilometria/métodos , Pletismografia/métodos , Testes de Função Respiratória/métodos , Espirometria/métodos , Volume de Ventilação Pulmonar/efeitos dos fármacos , Teste de Caminhada/métodosRESUMO
OBJECTIVE: To evaluate the plasma and aqueous humor disposition of prednisolone after oral administration in cats. METHODS: Six cats were administered with a single oral dose of prednisolone (10 mg). Blood and aqueous humor samples were serially collected after drug administration. Prednisolone concentrations in plasma and aqueous humor were measured at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 5.0 h after administration by a high-performance liquid chromatographic analytical method developed and validated for this purpose. RESULTS: Mean ± standard error (SE) of maximum plasma prednisolone concentration (300.8 ± 67.3 ng/mL) was reached at 1 h after administration. Prednisolone was distributed to the aqueous humor reaching a mean peak concentration of 100.9 ± 25.5 ng/mL at 1.25 h after administration. The mean ± SE systemic and aqueous humor exposure (AUC) was 553.3 ± 120.0 ng h/mL and 378.8 ± 64.9 ng h/mL, respectively. A high AUC(aqueous humor)/AUC(plasma) ratio was observed (0.68 ± 0.13). The mean half-life time of elimination in plasma and aqueous humor was 0.87 ± 0.16 h and 2.25 ± 0.44 h, respectively. CLINICAL SIGNIFICANCE: The observed high ratio between aqueous humor and plasma prednisolone concentrations indicates that extensive penetration of prednisolone to the anterior segment of the eye may occur. This is the first step that contributes to the optimization of the pharmacological therapeutics for the clinical treatment of uveitis.
Assuntos
Humor Aquoso/efeitos dos fármacos , Prednisolona/sangue , Prednisolona/farmacologia , Administração Oral , Animais , Gatos , Cromatografia Líquida de Alta Pressão , Masculino , Prednisolona/administração & dosagem , Prednisolona/farmacocinética , Reprodutibilidade dos Testes , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacosRESUMO
Cell encapsulation, although a promising strategy to deliver therapeutic products, is hampered by immune response against biomaterials. The aim of this article is to assess the effect of prednisolone on enzyme release by microencapsulated cells implanted in vivo. Recombinant cells encapsulated were implanted in the peritoneum of wild-type mice and mucopolysaccharidosis (MPS) I mice, with or without prednisolone. Later, microcapsules were recovered for histological and enzyme analysis. Blood was collected from MPS I mice. All animals receiving prednisolone had a smaller inflammatory infiltrate. In vitro, prednisolone increased the amount of enzyme released from the recovered capsules, but this was not accompanied by an increase in the amount of circulating enzyme in vivo after 15 days. However, in 7 days, prednisolone significantly increased the amount of enzyme detected in the serum. Although prednisolone improved enzyme release in vitro and in vivo after 7 days, it was unable to maintain this effect for a longer period.
Assuntos
Anti-Inflamatórios/farmacologia , Terapia de Reposição de Enzimas/métodos , Iduronidase , Mucopolissacaridose I/terapia , Prednisolona/farmacologia , Animais , Anti-Inflamatórios/farmacocinética , Linhagem Celular , Células Imobilizadas/transplante , Cricetinae , Feminino , Humanos , Iduronidase/biossíntese , Iduronidase/genética , Iduronidase/farmacocinética , Iduronidase/uso terapêutico , Camundongos , Mucopolissacaridose I/enzimologia , Mucopolissacaridose I/patologia , Prednisolona/farmacocinéticaRESUMO
To develop limited-sampling strategy (LSS) models for estimating prednisolone's area under plasma concentration versus time curve (AUC(0-infinity)), its maximum concentration in plasma (C(max)), and total clearance (CL/F). Healthy subjects (n = 24), enrolled in a bioequivalence study, received 20 mg PO of the prodrug prednisone as reference and test tablets, and plasma prednisolone concentrations (n = 576) were measured by a validated HPLC assay. A linear regression analysis of AUC(0-infinity), C(max), CL/F, and log(CL/F) against the plasma prednisolone concentrations for the reference formulation was carried out to develop LSS models to estimate these parameters. The LSS models were validated on the test formulation data sets and on simulated sets generated by the software ADAPT II. LSS models based on a single [1.5 hours for C(max) and 7 hours for AUC(0-infinity), CL/F, and log(CL/F)] plasma sample, accurately estimated (R2 = 0.84-0.97, mean bias < 1%; mean precision < 10%) these pharmacokinetic parameters. Validation tests indicated that the most informative single-point LSS models developed for the reference formulation provide precise estimates (R(2) > 0.83; mean bias < 3%; mean precision < 10%) of the corresponding pharmacokinetic parameters for the test formulation. LSS models based on the two most informative sampling points (1.5 and 7 hours) were required for accurate estimates (R(2) > 0.87; mean bias < 6%; mean precision < 8%) of prednisolone's C(max), AUC(0-infinity), CL/F, and log(CL/F) for the simulated data sets. Finally, bioequivalence assessment of the prednisone formulations, based on LSS-derived AUC(0-infinity) and C(max) values provided results identical to those obtained using the original values for these parameters. One- and 2-point LSS models provided accurate estimates of prednisolone's C(max), AUC(0-infinity), and CL/F, following single oral doses of prednisone, and allowed correct assessment of bioequivalence between two prednisone formulations.
Assuntos
Glucocorticoides/farmacocinética , Prednisolona/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Glucocorticoides/sangue , Meia-Vida , Humanos , Masculino , Taxa de Depuração Metabólica , Modelos Biológicos , Prednisolona/sangue , Reprodutibilidade dos Testes , Projetos de Pesquisa , Tamanho da Amostra , Equivalência TerapêuticaRESUMO
Prednisolone has unknown growth-suppressing effects relative to other steroids. We retrospectively studied 9 children (6 with congenital adrenal hyperplasia, CAH) receiving hydrocortisone replacement after switching to prednisolone (dose ratio, 1:5). Growth velocity and, in patients with CAH, 17-OHP decreased significantly. Dose reduction reversed these effects. Roughly, growth suppression relative potency for prednisolone:hydrocortisone was 15:1.
Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Insuficiência Adrenal/tratamento farmacológico , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Transtornos do Crescimento/induzido quimicamente , Hidrocortisona/farmacocinética , Hidrocortisona/uso terapêutico , Prednisolona/farmacocinética , Prednisolona/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidrocortisona/efeitos adversos , Lactente , Masculino , Prednisolona/efeitos adversos , Estudos Retrospectivos , Equivalência TerapêuticaRESUMO
Oral corticosteroids are as effective as intravenous therapy for treating acute exacerbations of asthma. They are available in tablets that can be crushed and mixed with soft food or syrup, and in a variety of liquid formulations that differ in volume required, palatability, patient acceptance, and cost. The most important consideration in product selection for a young child is that the doses can be easily swallowed and retained.
Assuntos
Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Dexametasona/administração & dosagem , Metilprednisolona/administração & dosagem , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Doença Aguda , Administração Oral , Anti-Inflamatórios/farmacocinética , Asma/prevenção & controle , Disponibilidade Biológica , Criança , Dexametasona/farmacocinética , Glucocorticoides/administração & dosagem , Humanos , Metilprednisolona/farmacocinética , Prednisolona/farmacocinética , Prednisona/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , PaladarRESUMO
Rapid glucocorticoid clearance and abnormal glucocorticoid receptor binding have been described as factors that contribute to an inadequate response to treatment with glucocorticoids in patients with asthma. We report the coexistence of these abnormalities in children with severe asthma who respond poorly to systemic glucocorticoid therapy.
Assuntos
Asma/tratamento farmacológico , Metilprednisolona/farmacocinética , Prednisolona/farmacocinética , Receptores de Glucocorticoides , Adolescente , Asma/metabolismo , Criança , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Metilprednisolona/uso terapêutico , Prednisolona/uso terapêuticoRESUMO
Prednisolone pharmacokinetics were evaluated in eight patients with cystic fibrosis (CF) (aged 1.8 to 20 years) by assessing absorption of orally administered prednisone (in its active form, prednisolone) and elimination of prednisolone after intravenous administration. After an overnight fast, subjects received intravenously administered doses of prednisolone or orally administered doses of prednisone, 40 mg/1.73 m2 body surface area, before a standardized breakfast. Serial blood samples were collected for 12 hours and analyzed for prednisolone concentration. Prednisolone pharmacokinetics were compared in eight age-matched patients with asthma who required steroids after intravenous administration of prednisolone. The prednisolone pharmacokinetic parameters derived demonstrated an increased total clearance (by 60%), an increased volume of distribution (by 46%), a lower peak concentration (by 35%), and no difference in elimination half-life in patients with CF compared with those with asthma. Bioavailability averaged 88.4% +/- 20.1% of the administered dose. Prednisolone clearance was markedly increased in those with CF. There was a proportional increase in nonrenal clearance, with no difference in renal clearance in those with asthma or CF. The plasma protein binding of prednisolone was only slightly decreased in patients with CF and did not account for the observed pharmacokinetic alteration. The marked increase in prednisolone clearance may necessitate the use of more frequent or higher doses of this steroid in the treatment of patients with CF, leading to a potentially less favorable benefit/risk ratio.
Assuntos
Fibrose Cística/metabolismo , Prednisolona/farmacocinética , Administração Oral , Asma/metabolismo , Disponibilidade Biológica , Criança , Humanos , Infusões Intravenosas , Prednisona/farmacocinéticaRESUMO
En el presente trabajo, se ha sometido a comparación fisicoquímica a tabletas de administración peroral conteniendo prednisona 5mg. como principio activo, comercializada actualmente en el Perú. Además se hace una comparación entre el medio de disolución exigido por la farmacopea, agua, con jugo gástrico. Los ensayos se han realizado de acuerdo a exigencias de la USP XXII. De los cinco productos analizados se demuestra que los correspondientes a la clave B, C, D y E son potencialmente equivalentes por presentar homogenicidad en la disolución de lote y en la uniformidad de contenido. El producto A no cumple con las especificaciones requeridas. No se encontró significado estadístico entre las diferencias de los valores medios de agua y jugo gástricos para cada producto respectivamente, lo cual indica que los resultados dados para ambos casos son válidos. Se hace incapié sobre la importancia de la biodisponibilidad de los medicamentos y la necesidad de efectuar el ensayo de devolución a éstos para garantizar su biodisponibilidad.