ABSTRACT
OBJECTIVE: To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon beta treatment as response indicators in multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS were followed during the first 2 years of treatment. Neurological assessments were performed every 3 months or when a relapse was suspected. MRI scans performed at baseline and at 3, 4, 5 and 6 months after the start of treatment were assessed centrally for disease activity: new T2 or gadolinium enhancing T1 lesions. NAb were assessed using the MxA protein assay; positivity was defined as two consecutive titres >or=20 NU/ml. We evaluated the predictivity of an active scan, NAb positivity, or both, during the first 6 months of treatment, on the occurrence of clinical disease activity in the following 18 months. RESULTS: 147 patients were assessed at 16 centres. Predictivity parameters (with confidence intervals) were as follows: active scan, sensitivity (SN) 52% (34-69%), specificity (SP) 80% (65-91%), negative predictive value (NPV) 73% (58-77%), positive predictive value (PPV) 62% (42-79%), p = 0.002; NAb positivity, SN 71% (45-88%), SP 66% (55-76%), NPV 92% (82-97%), PPV 29% (16-45%), p = 0.01; active scan and NAb positivity, SN 71% (38-91%), SP 86% (73-94%), NPV 94% (86-98%), PPV 50% (29-70%), p = 0.0003. CONCLUSIONS: MRI activity and NAb occurrence during the first 6 months of interferon beta treatment were reliable predictors of long term clinical response, particularly when combined. Patients with negative predictors showed a less than 10% risk of developing clinical activity. Patients with positive predictors showed a 50% risk of further clinical activity. These patients need to be followed carefully with further MRI and NAb tests.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Neurologic Examination/drug effects , Neutralization Tests , Adult , Antibodies/blood , Brain/drug effects , Brain/pathology , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Injections, Subcutaneous , Interferon beta-1b , Interferon-beta/immunology , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/immunology , Prospective Studies , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use , Treatment OutcomeSubject(s)
Anti-Infective Agents/pharmacokinetics , Buffaloes/metabolism , Cattle/metabolism , Sulfamethazine/pharmacokinetics , Animals , Animals, Newborn/metabolism , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/blood , Area Under Curve , Infusions, Intravenous/veterinary , Injections, Intravenous/veterinary , Male , Species Specificity , Sulfamethazine/administration & dosage , Sulfamethazine/bloodABSTRACT
O perfil do meclofenamato sódico, uma droga antiinflamatória não-esteroidal, foi determinado em seis bezerros pré-ruminantes após administração intravenosa e intramuscular na dose de 2,2mg/kg de peso vivo. As concentrações de meclofenamato foram medidas empregando-se cromatografía líquida de alta performance. A farmacocinética do meclofenamato sódico, após as administrações intravenosa e intramuscular, caracterizou-se por rápida fase de distribuição (t½a ), 15,45±4,85min e 23,14± 7,24min para a administração intravenosa e intramuscular, respectivamente, seguida por longa fase de eliminação (t½b ), após a aplicação intramuscular (17,55±6,52h.). O volume aparente de distribuição (Vd) da administração intravenosa da droga foi moderado (0,72±0,12l/kg), e após um lapso da aplicação intramuscular, foi alta (3,51±1,05l/kg). Isso pode ser explicado pelo efeito flip-flop ou por evitar a via enteroépatica. A biodisponibilidade obtida após administração intramuscular foi de 61 por cento.
Subject(s)
Animals , Male , Anti-Inflammatory Agents, Non-Steroidal , Meclofenamic Acid/pharmacokinetics , Cattle/metabolism , Anti-Inflammatory Agents, Non-Steroidal , Meclofenamic Acid/administration & dosage , Meclofenamic Acid/blood , Chromatography, High Pressure Liquid , Cross-Over Studies , Injections, Intramuscular , Injections, Intravenous , Statistics, Nonparametric , Time FactorsABSTRACT
Sixty 3-month-old homozygote male mice were studied for circadian rhythmicity in the toxicity of florfenicol overdose. Animals were kept under a regimen of 12h light, 12h darkness (12:12 LD) with food and water available ad libitum. The LD50 (median lethal) dose was determined in a preliminary experiment and was administered to groups of 10 mice at six different clock times (hours) after light onset (HALO): 0, 4, 8, 12, 16, and 20 HALO. Cosinor analysis verified a statistically significant (P < .04) circadian rhythm in the toxic effect (mortality) of florfenicol. Mortality was greatest when the drug was injected 4h after the commencement of the activity span (16 HALO) and least when injected 4h after the start of the diurnal rest span (4 HALO). Mortality was 2.5 times greater when drug injection was given at 16 HALO than at 4 HALO.
Subject(s)
Anti-Bacterial Agents/pharmacology , Circadian Rhythm , Thiamphenicol/analogs & derivatives , Thiamphenicol/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Overdose , Homozygote , Light , Male , Mice , Time FactorsABSTRACT
The plasma pharmacokinetics for a single intravenous dose (10 mg/kg body weight) of miocamycin (a 16-membered macrolide drug) was investigated in Holando Argentino cattle (n = 5). Blood drug concentrations were determined by a microbiological method and data were best-fitted to a two-compartment open model. The pharmacokinetic profile consisted of a short distribution phase (t1/2 alpha = 7.41 +/- 0.53 min), followed by an extended terminal elimination phase (t1/2 beta = 2.49 +/- 0.23 h). The volume of distribution at steady-state was large (2.13 +/- 0.17 l/kg), suggesting extensive tissue distribution, the clearance value was 0.60 +/- 0.03 l/h.
