Micro two‐dimensional electrophoresis in the absence of denaturing agents allowed the analysis of the multiple forms of serum aminopeptidases, including their multimolecular complexes, and the detection of their enzymatic activity towards different substrates. Two forms of alanine aminopeptidase (E.C. 3.4.11.2.), differing in sialic acid content, were detected in sera of healthy subjects. In sera of patients with hepatobiliary diseases a large number of additional spots was observed, some of them identified as multimolecular complexes, probably formed by an amphiphilic form of alanine aminopeptidase. Papain treatment resulted in the dissociation of the complexes and in the appearance of a light form of the enzyme in normal sera, which was otherwise only present in pathological samples. Additional spots corresponding to cysteine aminopeptidase (E.C. 3.4.11.3.) were detected in pregnancy sera.
Because numerous substances, endogenous compounds as well as xenobiotics, interfere with determination of uric acid and creatinine, we have devised a more nearly specific method by which we can simultaneously determine uric acid and creatinine in plasma by "high-performance" liquid chromatography. We used a mobile phase of ammonium acetate (30 mmol/L) and methanol (156 mmol/L) at pH 7.0 and a flow rate of 1 mL/min. We used a C18 reversed-phase column, and measured absorbance at 235 nm, the wavelength corresponding to the absorption maximum of uric acid and creatinine. Uric acid and creatinine could be determined in less than 5 min by directly injecting plasma diluted fivefold; use of a precolumn eliminated the need for deproteinization. We evaluated the precision, recovery, linearity, specificity, and limit of detection of the method and we checked for analytical interference by 37 currently used drugs. We compared results with those obtained by routine and reference methods.
1. The pharmacokinetics of nilvadipine in male and female rats, and in male mice, rabbits and dogs were studied after i.v. and oral dosing. 2. After i.v. dosing (0.1 mg/kg), the plasma concentrations of nilvadipine declined two- or three-exponential with terminal half-lives of 0.73 h in mice, 1.2 h in male and female rats, 3.7 h in rabbits and 5.0 h in dogs. Sex difference in pharmacokinetics after i.v. dosing in rats was not found. The systemic plasma clearance was in the order of mice greater than rats greater than rabbits greater than dogs, and nearly equalled the hepatic blood flow in each species. The volume of distribution at steady-state was high (greater than 4 L/kg) in all species. 3. After oral dosing, plasma concentrations of nilvadipine peaked within 1 h in all species except for middle and higher doses (4 and 16 mg/kg) in dogs. The area under the plasma concentration-time curves in male rats (3.2-100 mg/kg) and dogs (1-16 mg/kg) increased in proportion to the dose. Bioavailability was low in male rats (3-4%) and rabbits (2%), but in other species was 29-44%. The oral clearance in male rats was about 8 times higher than in female rats. 4. The free fraction of nilvadipine in plasma was 1.94% in mice, 1.89% in rabbits and 0.85% in dogs, with no dependence on plasma concentration over a range of 10-100 ng/ml.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.