ABSTRACT
To assess dose proportionality of etoricoxib across the anticipated clinical dose range, a single panel of 12 healthy subjects was administered single oral doses of etoricoxib of 5, 10, 20, 40, and 120 mg in an open, two-part, five-period crossover study. Plasma samples were collected aftereach dose and analyzed for etoricoxib concentrations. The pharmacokinetics of etoricoxib appear to be linear over the entire dose range examined, from 5 to 120 mg. Etoricoxib was found to be well tolerated across the 5 to 120 mg dose range.
Subject(s)
Cyclooxygenase Inhibitors/administration & dosage , Isoenzymes/antagonists & inhibitors , Pyridines/administration & dosage , Sulfones/administration & dosage , Administration, Oral , Adult , Analysis of Variance , Area Under Curve , Cross-Over Studies , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/adverse effects , Cyclooxygenase Inhibitors/blood , Dose-Response Relationship, Drug , Etoricoxib , Female , Humans , Male , Membrane Proteins , Prostaglandin-Endoperoxide Synthases , Pyridines/adverse effects , Pyridines/blood , Sulfones/adverse effects , Sulfones/bloodABSTRACT
Initial clinical trials with ivermectin were performed in patients with both roundworm infestation and onchocerciasis. Obvious clinical safety allowed for rapid progression through 5-30-50-100-150-200 mcg/kg in infected patients. Initial studies showed some effect at 50 mcg/kg; subsequent double-blind controlled studies, either with placebo or diethylcarbamazine (DEC), confirmed the efficacy of ivermectin as well as further defining its safety profile. Absence of adverse eye findings or serious systemic reactions justified the further open trials. Studies of patients treated at 6, 12, or 18 month intervals showed a long lasting effect of ivermectin in reducing skin microfilaria counts. Phase III studies confirmed safety and efficacy and further refined the dose to 150 mcg/kg every 12 months. Large trials in Liberia and other countries in West Africa, and subsequently under Onchocerciasis Control Program (OCP), included approximately 120,000 persons carefully followed during which few patients with serious adverse experiences were reported. These extensive field trials confirmed the relative safety allowing for broad distribution of ivermectin in programs not able to provide physician monitoring.
Subject(s)
Ivermectin/therapeutic use , Onchocerciasis/drug therapy , Animals , Clinical Trials as Topic , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Ivermectin/administration & dosage , Ivermectin/adverse effects , Onchocerca/isolation & purification , Onchocerciasis/parasitology , Skin/parasitologyABSTRACT
A 4-week, double-blind, controlled multi-centre study was carried out in 235 patients with active rheumatoid arthritis to compare the efficacy and tolerance of 500 mg or 1000 mg diflunisal per day administered once daily, in the evening, or in divided, twice daily dosage. The results showed that diflunisal given once daily was at least as effective as diflunisal given twice daily. Day pain, morning stiffness, average grip strength and erythrocyte sedimentation rate improved similarly in both groups. Significant differences favouring the once-daily regimen were observed for improvement in night pain, Ritchie index and overall assessments by patient and investigator. Adverse experiences were slightly more common in patients taking diflunisal once daily (24% vs 19%) but this difference was not significant. It is concluded, therefore, that diflunisal once-a-day is an alternative regimen for the treatment of rheumatoid arthritis. It is at least as effective as the twice-daily regimen and may provide additional convenience to the patient and potential enhancement of compliance.
