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S J Vetticaden

Publications and source records attributed to S J Vetticaden.

6 recordsLinked to original sources
PubMed1990

Chromatography of cardiac glycosides.

Most of the recently reported methods for the quantitation of cardiac glycosides have been for digoxin and its metabolites. Recent procedures using high-performance liquid chromatography-radioimmunoassay (HPLC-RIA) and HPLC following derivatization show appreciable improvements in accuracy and specificity for quantitating digoxin in the low nanogram range. Gas chromatographic procedures have been explored to a very limited extent and further advances in the quantitation of cardiac glycosides are anticipated to arise from the use of laser desorption-Fourier transform mass spectrometry. However, currently, HPLC with derivatization and HPLC-RIA techniques remain the techniques of choice for quantitation of digoxin and/or its metabolites based on considerations of ease of use, sensitivity, specificity, accuracy and reproducibility.

Cardiac Glycosides↗
PubMed1989

Pharmacodynamic modeling of digoxin-induced bradycardia.

Digoxin-induced bradycardia in dogs was used to evaluate several pharmacodynamic models. Digoxin plasma concentrations and response were monitored in beagle dogs administered either 0.05 or 0.025 mg/kg of digoxin iv as an infusion over 5 min. The models investigated were the linking model, the linear model, the effect compartment model, and the inhibitory model. Regression procedures for investigating the effect compartment model were conducted with Emax (the maximal response, where response was the percentage decrease in heart rate) as a variable with an upper bound of 100%, with a constant value of 100%, or alternately with a constant value equal to the maximal observed response. Based on statistical criteria the effect model using Emax as a variable was found to be the best model for describing digoxin-induced bradycardia. For the effect compartment model, CPss(50) (concentration at steady state that will produce 50% of the maximal response) ranged from 3.8-9.8 ng/ml; delta (exponent describing the steepness of the concentration-response relationship) ranged from 0.6-7.1. The implication of these models in understanding concentration-effect relationships are discussed.

Animals↗
PubMed1989

Phenotypic differences in dextromethorphan metabolism.

Polymorphic differences in dextromethorphan metabolism were observed in three studies conducted in a total of 44 subjects (of Dutch origin) administered 60 mg dextromethorphan hydrobromide as an OROS tablet. Mean plasma dextromethorphan (DM) concentrations after a single dose and at steady state were 4-75 times higher in the poor metabolizers (PM) relative to the extensive metabolizers (EM). Following a single dose, the mean areas under the plasma concentration-time curve (AUC, 0-24 hr) of DM, total dextrorphan (DR), and total 3-hydroxymorphinan (HM) were 6.9-fold higher, 17.4-fold lower, and 11-fold lower, respectively, for the PM than for the EM. Correspondingly, steady-state AUC values were 52.8 times higher, 6.7 times lower, and 3.3 times lower for DM, total DR, and total HM, respectively, for the PM relative to the EM. Drug/metabolite ratios (DMR) for amounts excreted in the urine of DR and HM indicated polymorphism in O-demethylation of DM since DMR for PM was 352 and 338 times higher than that for EM for DR and HM, respectively. However, polymorphism in N-demethylation was not observed. Ratios of conjugated/free dextrorphan and 3-hydroxymorphinan excreted in the urine suggest also a lack of conjugative capacity in the PM, relative to the EM. The overall incidence of PM was 9.1% in this population.

Administration, Oral↗
PubMed1988

Polymorphic differences in drug metabolism and response.

Genetic differences in drug metabolism and response, also referred to as pharmacogenetic differences, result in polymorphism in the pharmacokinetics and pharmacodynamics of a drug. Acetylation and debrisoquin oxidation have been extensively studied by investigators in order to identify the geographical distribution of these polymorphic differences in drug metabolism. Metabolic pathways for various drugs have been correlated with debrisoquin metabolism, the observed polymorphism being attributed to variants of cytochrome P-450. Medical recognition of these polymorphic differences in drug disposition is vital because of clinical manifestations arising from these differences. Deficiencies in metabolic pathways enhance susceptibility to adverse reactions but reduce the susceptibility to chemical carcinogenesis. Therapeutic success or failure may result from concomitant administration of drugs that undergo metabolism via pathways with co-regulated genetic polymorphism and is, therefore, an important consideration in the treatment of any population of varying ethnic proportions. Anomalous metabolism and response to a drug should be investigated with innocuous probes, e.g., dextromethorphan or antipyrine at low doses, and if possible, correlated to metabolic pathways that have been previously identified as demonstrating genetic polymorphism.

Chemistry, Pharmaceutical↗