RESUMO
To develop a population pharmacokinetic model that describes the absorption and low plasma levels of risedronate in the body. The impact of patients' characteristics on risedronate kinetics is investigated. Simulations revealed the high variability in the concentration levels after different dosage schemes. No dosage adjustment is required in renal impairment. INTRODUCTION: Risedronate exhibits very low plasma levels and high residence time in the body. The aim of this study is to describe and explain the risedronate transit through the body. The impact of volunteers' characteristics on the kinetics of risedronate is also investigated. Simulations are used to compare the risedronate plasma levels after different dosage schemes and assess the need for dose adjustment in patients with impaired kidney functionality. METHODS: Plasma concentration-time data were obtained from a four-period, two sequence, single-dose, crossover bioequivalence study. The effects of several covariates (e.g., weight, albumin, creatinine, alkaline phosphatase, and calcium) on model parameters were tested. Non-linear mixed-effect modeling was applied and a variety of models were evaluated placing emphasis on absorption and disposition properties. The modeling and simulation work was implemented in MonolixTM 2020R1. RESULTS: Following oral administration, the kinetics of risedronate was best described by a two-compartment model with lag time, first-order absorption, and elimination. The extent of peripheral distribution (i.e., bones) was found to be remarkably high. No volunteer characteristics were identified to affect significantly the disposition of risedronate. Using simulations, risedronate plasma profiles were obtained for different doses and frequencies of administration. CONCLUSION: The absorption and disposition kinetics of risedronate were successfully characterized. Simulations revealed the high discrepancy in the concentration levels observed after different dosage regimens, implying the safety profile of risedronate. In virtual patients with renal impairment, the blood levels of risedronate are increased, but not in an extent requiring dose adaptation.
Assuntos
Osteoporose , Insuficiência Renal , Administração Oral , Estudos Cross-Over , Humanos , Modelos Biológicos , Osteoporose/tratamento farmacológico , Ácido RisedrônicoRESUMO
The aim of our study was to evaluate the association between the mammographic appearance and the biologic characteristics of high-grade breast carcinomas. Three hundred and twenty patients with breast carcinomas were studied. Histological examination showed 83 (26%) high-grade ductal carcinomas. Immunohistochemistry was carried out by using antibodies against estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53 and cathepsin D. In 60/83 high-grade carcinomas we studied the mammographic appearance. Asymmetric density with poorly defined margins without microcalcifications was the major mammographic finding in 49/60 (approximately 82%) high-grade ductal carcinomas. HER-2/neu positivity (68.7%) and p53 positivity (48.2%) were statistically correlated with asymmetric density with poorly defined margins without microcalcifications in high-grade carcinomas. We observed loss of ER and PR receptors in 50%, whereas loss of PR receptors was observed in 65% of high-grade breast carcinomas. Cathepsin D (> 20%) was detected in 38.5% of high-grade carcinomas. Our findings suggest a significant relationship between mammographic appearance and biologic markers in high-grade breast carcinomas.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Regulação Neoplásica da Expressão Gênica , Mamografia , Adulto , Idoso , Biomarcadores Tumorais/análise , Biópsia por Agulha , Neoplasias da Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Catepsina D/metabolismo , Estudos de Coortes , Feminino , Genes p53 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Biologia Molecular , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Sensibilidade e EspecificidadeRESUMO
Congenital muscular dystrophy (CMD) is a heterogeneous group of neuromuscular disorders characterized by muscle weakness and hypotonia at birth or within the first few months of life. It is inherited in an autosomal recessive pattern. About half of the patients have a deficiency of the alpha-2-chain of laminin (merosin). We describe a case of congenital muscular dystrophy in an infant with laminin-a2-chain deficiency, which appeared hypotonia in early infancy. Diagnosis was made by clinical features and the histological and immunohistochemical studies on muscle biopsy.
Assuntos
Laminina/deficiência , Distrofias Musculares/congênito , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Músculos/patologia , Distrofias Musculares/diagnóstico , Distrofias Musculares/patologiaRESUMO
We prospectively evaluated the incidence of gallbladder pseudolithiasis in children treated with high doses of ceftriaxone for a variety of serious infections. We also monitored the time interval needed for this phenomenon to develop and resolve completely after initiation and cessation of treatment, respectively. Included in this study are 44 children treated with ceftriaxone 100 mg/kg/d divided into 2 equal intravenous doses and followed by serial abdominal sonography. Eleven children developed pseudolithiasis of gallbladder 2-9 d after initiation of ceftriaxone therapy. Six children (54.5%) developed this complication within the first 3 d. Lithiasis completely resolved 8-23 d after the end of treatment. In conclusion, pseudolithiasis of the gallbladder developed in 25% of sick children and completely resolved in all patients. Early development of this complication was not exceptional. It occurred in more than half of these children.
Assuntos
Ceftriaxona/efeitos adversos , Cefalosporinas/efeitos adversos , Colelitíase/induzido quimicamente , Adolescente , Ceftriaxona/administração & dosagem , Ceftriaxona/uso terapêutico , Cefalosporinas/administração & dosagem , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Colelitíase/diagnóstico por imagem , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Tempo , Ultrassonografia , Bexiga Urinária/diagnóstico por imagemRESUMO
OBJECTIVE: The purpose of the study is to determine whether the 810-nm diode wavelength using a rectangular waveform is clinically effective in the treatment of choroidal neovascularization from age-related macular degeneration and to determine whether macular edema secondary to branch vein occlusion or diabetic retinopathy can be effectively treated with this laser using the micropulse waveform. DESIGN: Review of consecutive nonrandomized patients whose eyes were treated with the diode laser over a 30-month period. PARTICIPANTS: Fifty-three patients with an initial presentation of choroidal neovascularization located subfoveally (77%), extrafoveally (17%), and juxtafoveally (6%); 14 patients with macular edema from a branch vein occlusion; and 59 patients with diabetic macular edema, 40 of which were treated for the first time. INTERVENTION: Ablative rectangular wave laser photocoagulation was applied to the choroidal neovascular membranes and very light threshold treatment was applied in a macular grid to treat retinal edema. Microaneurysms were not targeted. MAIN OUTCOME MEASURES: Anatomic resolution of macular edema or choroidal neovascularization and visual acuity. RESULTS: Sixty percent of eyes treated for choroidal neovascularization had no persistence or recurrence at 6 months, and 72% achieved visual stabilization. In 8% of eyes, some localized bleeding occurred during photocoagulation. Clinical resolution of macular edema from branch vein occlusion occurred by 6 months in 92% of eyes, and 77% had stabilization of visual acuity. At 6 months, 76% of newly treated patients with diabetic macular edema and 67% of previously treated patients had clinical resolution of their edema. Vision was improved or stabilized in 91% and 73% of newly treated and retreated patients at 6 months, respectively. CONCLUSIONS: The micropulsed 810-nm diode laser is clinically effective in the treatment of macular edema from venous occlusion and diabetic retinopathy, and the rectangular (normal) mode diode laser can be used in many eyes with choroidal neovascularization.