ABSTRACT
A quantitative method based on radioimmunoassay for the determination of an endothelin receptor antagonist (C(31)H(33)NO(7), I) has been developed and validated. The immunogen was prepared by coupling I to the bovine serum albumin via the N-hydroxysuccinimide ester of I from which the radioligand was also prepared by the reaction with [125I]-iodotyrosine. The method was specific and no immunoactive material other than the parent drug was detectable in mammalian plasma. This direct assay, using 50 microl of rat plasma is sensitive (0.4 ng/ml), without matrix interference, and has sufficient sensitivity, specificity, accuracy and precision for the analysis of dosed rat plasma samples.
Subject(s)
Endothelin Receptor Antagonists , Pharmaceutical Preparations/blood , Animals , Dose-Response Relationship, Drug , Female , Male , Pharmaceutical Preparations/chemistry , Protein Binding/physiology , Rabbits , Radioimmunoassay/methods , RatsABSTRACT
A quantitative method based on radioimmunoassay for the determination of the antifungal agent, CANCIDAS (MK-0991) has been developed and validated. The immunogen was prepared by coupling MK-0991 to bovine serum albumin through a two-step reaction with difluorodinitrobenzene. An antiserum specific to MK-0991 was selected for RIA. The assay was based on the competitive immunoassay principle in which the drug competes with iodinated drug for a limited quantity of specific antibody. The bound tracer was separated via goat anti-rabbit globulin. The assay demonstrates good accuracy and reproducibility at plasma concentration down to 10 ng/ml. The specificity of the RIA method was confirmed by cross-validating against an established HPLC method.
Subject(s)
Anti-Bacterial Agents/blood , Peptides, Cyclic , Peptides , Radioimmunoassay/methods , Animals , Anti-Bacterial Agents/metabolism , Caspofungin , Echinocandins , Lipopeptides , Rabbits , Radioligand Assay , Reproducibility of Results , Sensitivity and Specificity , Serum Albumin, Bovine/metabolismABSTRACT
BACKGROUND: Enalapril in RAPIDISC* (wafer), a new easy-to-administer formulation of enalapril, may improve the convenience of enalapril therapy, thereby helping patients adhere to antihypertensive treatment. SUBJECTS AND METHODS: To determine whether 20 mg enalapril wafer is bioequivalent to the conventional 20 mg enalapril tablet, an open-label, two-period crossover study was performed in 16 healthy male volunteers. Cumulative urinary recovery of free enalaprilat (active metabolite of enalapril) and the serum maximum concentration of free enalaprilat (Cmax) were the primary pharmacokinetic parameters used to determine bioequivalence in this study. Bioequivalence was defined as the geometric mean ratio (wafer: tablet) falling within the equivalence limits of 0.80 to 1.25 for both parameters. RESULTS: Cumulative urinary recovery of free enalaprilat (0 - 72 hours) was similar between the wafer and conventional tablet formulations (arithmetic mean 5.13 vs. 5.03 mg, about 36% of dose). The geometric mean ratio of the urinary recovery of free enalaprilat (wafer: tablet) was 1.03 (90% CI: 0.93, 1.15). Cmax of serum enalaprilat was also similar between the wafer and conventional tablet formulations (arithmetic mean 85.7 vs. 76.3 ng/ml). The geometric mean Cmax ratio (wafer: tablet) was 1. 10 (90% CI: 1.00, 1.22). Both enalapril formulations were well tolerated. CONCLUSION: This study demonstrates that 20 mg enalapril in RAPIDISC is bioequivalent to 20 mg enalapril conventional tablet.
