RESUMO
The aim of the investigation was to compare the effectiveness of two absorption enhancers, sodium caprate (C10) and sodium deoxycholate (SDC), in increasing the bioavailability of a poorly absorbed paracellar flux drug, berberine chloride, across the intestinal mucosae of rats in vivo, together with examination of their effects on mucosal damage. In addition, all four intestinal segments were collected after administration of the enhancers and sodium saline. The results of the bioavailability experiments showed the oral absorption of berberine chloride was poor and both C10 and SDC could significantly improve the very poor absorption of berberine chloride. After co-administration, the area under the plasma concentration-time curve of berberine chloride was increased 41.1-fold by C10 (100 mg/kg) and 35.3-fold by SDC (100 mg/kg) compared with that in the absence of C10 and SDC, respectively. Local toxicity experiment indicated that both enhancers caused no specific damage to the intact intestine. This study demonstrates that C10 and SDC could significantly promote the absorption of berberine chloride from the gastrointestinal tract with few toxic effects, which might be due mainly to relaxing the absorption limitation while inhibiting the efflux transporter of berberine chloride by the enhancers. Besides, this could lead to the development of new drug-enhancers.
Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Berberina/farmacocinética , Ácidos Decanoicos/química , Ácido Desoxicólico/química , Excipientes/química , Absorção Intestinal , Mucosa Intestinal/metabolismo , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/sangue , Antineoplásicos Fitogênicos/química , Berberina/efeitos adversos , Berberina/sangue , Berberina/química , Disponibilidade Biológica , Ácidos Decanoicos/efeitos adversos , Ácido Desoxicólico/efeitos adversos , Excipientes/efeitos adversos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Regulação para CimaRESUMO
Biologic agents (also termed biologics) have become an important adjuvant-targeted treatment option in autoimmune blistering disease. We evaluated the efficacy and safety of newly licensed biologics for the management of pemphigoid using a meta-analysis. PubMed, EMBASE, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with biological agents (rituximab, dupilumab, omalizumab, or mepolizumab) were searched. The pooled risk ratio (RR) with a 95% confidence interval (CI) was used to assess the short-term efficacy, adverse event (AE), relapse, and long-term survival. A total of seven studies involving 296 patients were identified. The pooled RRs for short-term effectiveness, AE, relapse, and long-term survival rate in patients treated with biological agents versus systemic corticosteroids were 1.37 (95% CI 0.95-1.97; I2 = 82%; P = 0.09), 0.54 (95% CI 0.39-0.73; I2 = 13%; P = 0.005), 1.36 (95% CI 0.95-1.96; I2 = 16.8%; P = 0.19), and 1.08 (95% CI 0.95-1.21; I2 = 48.1%; P = 0.53), respectively. Meta-regression and subgroup analysis revealed that the RRs of efficacy were 2.10 (95% CI 1.61-2.75; I2 = 0%; P < 0.00001) for rituximab and 2.07 (95% CI 1.61-2.67; I2 = 0%; P < 0.00001) for sample size greater than 30. Compared with conventional therapy, biologics treatment was significantly associated with fewer adverse events (P < 0.05), but no significant differences were found for efficacy and relapse (P > 0.05). The findings demonstrate that a biologics-containing regimen could minimize the occurrence of AEs and might display a comparable efficacy and recurrence to that of receiving systemic corticosteroids.
Assuntos
Produtos Biológicos , Penfigoide Bolhoso , Humanos , Rituximab/efeitos adversos , Fatores Biológicos , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/induzido quimicamente , Corticosteroides , Doença Crônica , Produtos Biológicos/efeitos adversos , RecidivaRESUMO
BACKGROUND: Condyloma acuminatum (CA) of the anal canal is difficult to treat and subject to relapse.. We investigated the effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with oral acitretin during therapy of refractory CA in the anal canal. We also conducted a clinical retrospective study for the treatment of intra-anal CA. METHODS: A total of 101 patients diagnosed with intra-anal CA were enrolled. All patients underwent liquid nitrogen cryotherapy as a basic treatment until visible wart clearance. Patients were divided into two groups depending on the treatment modality after cryotherapy. ALA-PDT group with 51 patients was given ALA-PDT treatment, and ALA-PDT plus acitretin group with 50 patients was given ALA-PDT treatment combined with oral acitretin. The cure rate, recurrence rate, and adverse reactions of the two groups were analyzed and recorded. RESULTS: The cure rate in the ALA-PDT plus acitretin group was 94% (47/50), which was significantly higher than 80.4% (41/51) in ALA-PDT group. The recurrence rate in the ALA-PDT plus acitretin group was 6% (3/50), which was lower than 19.6% (10/51) in ALA-PDT group (P<0.05). CONCLUSION: ALA-PDT combined with oral acitretin is effective and safe in the treatment of refractory CA in anal canal, and with further study may become an option for these patients.