intrinsic-factor and Syndrome

Rufinamide is a new, orally active antiepileptic drug (AED), which has been found to be effective in the treatment of partial seizures and drop attacks associated with the Lennox-Gastaut syndrome. When taken with food, rufinamide is relatively well absorbed in the lower dose range, with approximately dose-proportional plasma concentrations up to 1,600 mg/day, but less than dose-proportional plasma concentrations at higher doses due to reduced oral bioavailability. Rufinamide is not extensively bound to plasma proteins. During repeated dosing, steady state is reached within 2 days, consistent with its elimination half-life of 6-10 h. The apparent volume of distribution (V(d)/F) and apparent oral clearance (CL/F) are related to body size, the best predictor being body surface area. Rufinamide is not a substrate of cytochrome P450 (CYP450) enzymes and is extensively metabolized via hydrolysis by carboxylesterases to a pharmacologically inactive carboxylic acid derivative, which is excreted in the urine. Rufinamide pharmacokinetics are not affected by impaired renal function. Potential differences in rufinamide pharmacokinetics between children and adults have not been investigated systematically in formal studies. Although population pharmacokinetic modeling suggests that in the absence of interacting comedication rufinamide CL/F may be higher in children than in adults, a meaningful comparison of data across age groups is complicated by age-related differences in doses and in proportion of patients receiving drugs known to increase or to decrease rufinamide CL/F. A study investigating the effect of rufinamide on the pharmacokinetics of the CYP3A4 substrate triazolam and an oral contraceptive interaction study showed that rufinamide has some enzyme-inducing potential in man. Findings from population pharmacokinetic modeling indicate that rufinamide does not modify the CL/F of topiramate or valproic acid, but may slightly increase the CL/F of carbamazepine and lamotrigine and slightly decrease the CL/F of phenobarbital and phenytoin (all predicted changes were <20%). These changes in the pharmacokinetics of associated AEDs are unlikely to make it necessary to change the dosages of these AEDs given concomitantly with rufinamide, with the exception that consideration should be given to reducing the dose of phenytoin. Based on population pharmacokinetic modeling, lamotrigine, topiramate, or benzodiazepines do not affect the pharmacokinetics of rufinamide, but va

Topics: Administration, Oral; Adolescent; Age Factors; Anticonvulsants; Body Mass Index; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Epilepsy; Female; Food; Half-Life; Humans; Intrinsic Factor; Kidney Diseases; Liver Diseases; Male; Metabolic Clearance Rate; Renal Dialysis; Sex Factors; Syndrome; Triazoles

Topics: Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Female; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Hypothyroidism; Intrinsic Factor; Parietal Cells, Gastric; Sjogren's Syndrome; Syndrome; Thyroiditis, Autoimmune; Vitamin B 12 Deficiency; Xerostomia

Topics: Adolescent; Adult; Agammaglobulinemia; Anemia, Macrocytic; Anemia, Megaloblastic; Antibody Formation; Chronic Disease; Female; Gastric Juice; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male; Proteinuria; Syndrome; Vitamin B 12 Deficiency

Topics: Achlorhydria; Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Antibodies; Erythrocyte Count; Folic Acid; Histamine; Humans; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; Pentagastrin; Reticulocytes; Schilling Test; South Africa; Stimulation, Chemical; Syndrome; Tetracycline; Vitamin B 12

Topics: Addison Disease; Adolescent; Adult; Antibodies, Anti-Idiotypic; Autoimmune Diseases; Candidiasis; Diabetes Mellitus; Female; Follicle Stimulating Hormone; Gastritis; Humans; Hypoparathyroidism; Hypopituitarism; Intrinsic Factor; Luteinizing Hormone; Myxedema; Ovarian Diseases; Syndrome; Thyroiditis, Autoimmune

Topics: Adolescent; Adult; Age Factors; Aged; Anemia, Macrocytic; Anemia, Pernicious; Autoantibodies; Black or African American; Black People; Diagnosis, Differential; Ethnicity; Folic Acid; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; South Africa; Syndrome; Tetracycline; Vitamin B 12

Topics: Adult; Anemia, Macrocytic; Anemia, Pernicious; Bone Marrow; Bone Marrow Examination; Diagnosis, Differential; Female; Gastric Mucosa; Humans; Intrinsic Factor; Schilling Test; Syndrome

Topics: Adolescent; Anemia; Anemia, Pernicious; Chromosome Aberrations; Chromosome Disorders; Female; Genital Diseases, Female; Humans; Hypocalcemia; Hypoparathyroidism; Intrinsic Factor; Syndrome