intrinsic-factor and Kidney-Diseases

Gastric intrinsic factor (IF) secretion was examined in five patients with impaired renal function during stepwise increasing doses (0.02, 0.2, and 2.0 micrograms/kg/h) of intravenous infusion of pentagastrin alone or in combination with continuous intravenous infusion of cimetidine (05 mg/kg/h) after and initial bolus of 1.5 mg/kg. Whereas cimetidine caused a moderate reduction of maximally stimulated IF output, the output during submaximal stimulation was reduced to basal levels by cimetidine. The results suggest that IF insufficiency may occur during cimetidine treatment in patients with impaired renal function on long-term treatment with H2-blockers.

Topics: Adult; Cimetidine; Dose-Response Relationship, Drug; Gastric Acid; Humans; Intrinsic Factor; Kidney Diseases; Middle Aged; Pentagastrin; Pepsin A

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

A nonisotopic assay of vitamin B-12 in human serum or plasma is described, performed with the Abbott IMx analyzer. The sample is first treated at pH > 12.5 to release bound vitamin B-12 and to convert all forms to cyanocobalamin. Next, the analyte is bound, at lower pH, by vitamin B-12-specific binding protein, immobilized to a solid phase of polymeric microspheres. Detection involves monitoring the activity of the tracer enzyme (alkaline phosphatase) coupled to a derivative of cyanocobalamin. Total assay precision is 7.9% for vitamin B-12 at 200 ng/L, 6.6% at 400 ng/L, and 6.7% at 800 ng/L. Assay sensitivity, calculated as 2 SD from the zero calibrator, is 37 (+/- 9) ng/L. The dynamic range extends to 2000 ng/L. Analytical recovery of 300 and 600 ng/L additions of vitamin B-12 to sera with basal concentrations of 30-400 ng/L was 102.5%. Results of the assay correlated well with those of commercially available radioisotope assays. No interference was observed in specimens from patients with pernicious anemia, chronic or acute myelogenous leukemia, or renal failure. Cross-reactivity with cobinamide (1 g/L) was < 0.00003%. Vitamin B-12 measurements for blood specimens drawn into serum, EDTA, or heparinized plasma-collection tubes agreed within 3%.

Topics: Anemia, Pernicious; Animals; Autoanalysis; Humans; Hydrogen-Ion Concentration; Intrinsic Factor; Kidney Diseases; Leukemia, Myeloid, Acute; Quality Control; Swine; Vitamin B 12

Topics: Anemia, Pernicious; Cobalt Radioisotopes; Humans; Intestinal Absorption; Intrinsic Factor; Kidney Diseases; Malabsorption Syndromes; Methods; Time Factors; Vitamin B 12

Topics: Administration, Oral; Anemia, Pernicious; Cobalt Isotopes; Crohn Disease; Female; Humans; Intestinal Absorption; Intrinsic Factor; Kidney Diseases; Malabsorption Syndromes; Male; Methods; Schilling Test; Time Factors; Vitamin B 12