RESUMEN
OBJECTIVE: Phototherapy is the standard therapeutic approach for neonatal hyperbilirubinemia. Oxidative effects of phototherapy may have potential harms, including DNA damage. Unconjugated bilirubin (UCB) might also possess antigenotoxic potential. Intensive phototherapy is more efficacious than conventional phototherapy in treating hyperbilirubinemia. This study aimed to assess the impact of hyperbilirubinemia and the two different types of phototherapy on DNA damage in peripheral blood mononuclear cells of neonates. STUDY DESIGN: The study was conducted on term neonates with non-hemolytic hyperbilirubinemia and control healthy neonates. Genotoxicity was assessed using single-cell gel electrophoresis (Comet assay) in peripheral mononuclear cells. Blood samples were obtained at enrollment in all infants and after intensive or conventional phototherapy in jaundiced infants. RESULT: DNA damage did not significantly differ between jaundiced and non-jaundiced neonates (11.4±8.7 and 10.9±8.3 arbitrary units (AU), respectively, P=0.58). It increased significantly after exposure to phototherapy compared with prephototherapy values (45.6±14.7 vs 11.4±8.7 AU, respectively, P<0.001). The duration of phototherapy correlated positively with markers of DNA damage (r=0.86, P<0.001); however, the intensity of used light did not significantly impact genotoxicity. CONCLUSION: Hyperbilirubinemia does not influence DNA damage, whereas both conventional and intensive phototherapy are associated with DNA damage in term infants with hyperbilirubinemia.
Asunto(s)
Ensayo Cometa/métodos , Daño del ADN , Hiperbilirrubinemia Neonatal , Leucocitos Mononucleares , Fototerapia , Estudios de Casos y Controles , Femenino , Humanos , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Recién Nacido , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/fisiología , Masculino , Pruebas de Mutagenicidad/métodos , Fototerapia/efectos adversos , Fototerapia/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: There is a general concern about the use of multisource (generic) antibacterials in the clinical setting with registration based solely on bioequivalence data. In order to address this concern, two modified-release formulations of clarithromycin (i.e. the originator Klacid XL and the generic Klarithran MR) were compared in patients with acute community-acquired respiratory tract infections. METHODS: Patients presenting with tonsillopharyngitis, sinusitis or pneumonia were randomized to receive either of the test drugs provided they clinically qualified for empirical clarithromycin treatment. The study endpoints were clinical and bacteriological cure rates, tolerability and safety. The study was designed to test for non-inferiority with regard to cure rates. RESULTS: The main outcome of this study was that both agents had similar clinical (non-inferior) and bacteriological cure rates and demonstrated no difference in tolerability in patients. The study also demonstrated the clinical efficacy of clarithromycin when used as empirical treatment in patients with respiratory tract infections in community practice (i.e. 95% clinical cure rate). CONCLUSION: The clarithromycin extended-release multisource product (Klarithran MR) does not differ significantly from the originator (Klacid XL) and the clinical cure rate of the generic formulation is non-inferior to that of the originator. The two formulations are tolerated similarly.
Asunto(s)
Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Administración Oral , Adulto , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Claritromicina/efectos adversos , Claritromicina/farmacocinética , Infecciones Comunitarias Adquiridas , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/farmacocinética , Femenino , Humanos , Masculino , Estudios Prospectivos , Método Simple Ciego , Equivalencia Terapéutica , Resultado del TratamientoRESUMEN
This randomized, double-blind study compared the efficacy and safety of a 5-d course of the new ketolide antimicrobial, telithromycin, with those of a standard 10-d course of penicillin V (phenoxymethylpenicillin) in patients with group A beta-hemolytic streptococci (GABHS) pharyngitis/tonsillitis. Patients aged 15-65 y (n = 395) with clinical signs and symptoms of pharyngitis/tonsillitis and a positive streptococcal antigen test or throat culture for GABHS were randomized to receive either telithromycin 800 mg once daily for 5 d (n = 198) or penicillin V 500 mg three times daily for 10 d (n = 197). Clinical and bacteriologic outcomes were assessed at post-therapy, test-of-cure (Days 16-20) and late post-therapy (Days 38-45) visits. Telithromycin for 5 d was equivalent to 10 d of penicillin V in terms of bacteriologic and clinical outcome (per-protocol): at post-therapy, test-of-cure visit, bacteriologic outcome was satisfactory in 84.3% and 89.1% of patients in the telithromycin and penicillin V groups, respectively, while clinical cure was achieved in 94.8% and 94.1% of patients, respectively. At late post-therapy, 82.4% of patients treated with telithromycin achieved a satisfactory bacteriologic outcome, compared with 84.7% of penicillin V recipients. The GABHS eradication rates for telithromycin and penicillin post-therapy were 85.2% and 89.1%, respectively, and 86.1% and 86.5%, respectively at late post-therapy. Both treatments were well tolerated, with a similar overall incidence of treatment-emergent adverse events. Short-course (5 d) therapy with telithromycin 800 mg once daily is comparable to a standard 10 d course of penicillin V for the treatment of GABHS pharyngitis/tonsillitis in adults and adolescents.
Asunto(s)
Antibacterianos/uso terapéutico , Cetólidos , Macrólidos , Penicilina V/uso terapéutico , Penicilinas/uso terapéutico , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Tonsilitis/tratamiento farmacológico , Adolescente , Adulto , Método Doble Ciego , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Faringitis/microbiología , Tonsilitis/microbiología , Resultado del TratamientoRESUMEN
The serum levels and side effects of an acute oral loading dose-schedule of carbamazepine (CBZ) divitabs [CBZ controlled release (CR)] and phenytoin (PHT) were assessed in patients at risk of seizures. CBZ-CR and PHT were administered to 42 adult patients (21 each) at a dosage of 20 mg/kg with a minimum and maximum dosage of 1,200 and 1,600 mg in patients weighting < 60 and > 80 kg, respectively. CBZ-CR was given as single loading dose; PHT was split, with two thirds of the dose administered at 0 h and one third administered 2 h later. The 24- and 36-h doses were assessed according to the nystagmus status at 24 h. Mean CBZ serum levels (percentage of subjects with level > 4 micrograms/ml shown in parentheses) were 0.0 (0%), 5.2 (62%), 6.7 (81%), 6.8 (95%), and 6.1 micrograms/ml (95%) at 0, 4, 8, 24, and 48 h after loading, respectively, and mean PHT levels (percentage of subjects with PHT level > 10 micrograms/ml in parentheses) were 0.1 (0%), 13.2 (86%), 16.3 (100%), 16.3 (100%), and 15.4 micrograms/ml (82%). One subject in the CBZ group and 3 in the PHT group vomited. Clinical effects did not differ significantly between treatment groups and are reported. Acute doses of CBZ-CR 20 mg/kg and PHT 20 mg/kg (two-thirds at 0 h and one-third at 2 h) provided therapeutic levels in most patients in < or = 4 h and were well tolerated.