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Biomedical subjects

L A Siddoway

Publications and source records attributed to L A Siddoway.

23 records · Page 2Linked to original sources
PubMed1984

Potential applications of free drug level monitoring in cardiovascular therapy.

Cardiovascular drugs, as a class, have low therapeutic indices, but also have great therapeutic potential. Plasma concentration information is therefore often of value when using these drugs. Unfortunately, the total plasma concentration may not reflect the concentration of pharmacologically active free drug, since a number of factors including disease states, heparin anticoagulation, non-linear binding characteristics, and in vitro artefacts can affect the protein binding of these agents. This may also explain their poor dose-response relationships and great interindividual variability in plasma concentration data. Careful studies relating bound and free drug concentration to pharmacological response may provide the clinician with a better guide to therapy, and enhance the usefulness of these drugs.

Anti-Arrhythmia Agents↗
PubMed1983

Amiodarone dosing: a proposal based on its pharmacokinetics.

The available data concerning amiodarone dosing may be summarized as follows: (1) there is an empirically demonstrated improvement in lag before onset of antiarrhythmic effect if amiodarone is given initially in large "loading" doses. (2) A regimen such as that described in this article may allow more predictable and safe therapy and should be evaluated in patients, in order to develop uniform dosing guidelines. (3) Amiodarone clearance appears to decrease with time, and for this reason guidance of long-term therapy by plasma concentration determinations could potentially improve safety and efficacy. However, a close correlation between drug levels and drug toxicity and efficacy is lacking. (4) Finally, plasma concentrations, although potentially useful for monitoring long-term therapy, are likely to be unhelpful or misleading during the 4- to 6-week loading period at the beginning of treatment.

Amiodarone↗
PubMed1977

Purification of HLA-linked B lymphocyte alloantigens in immunologically active form by preparative sodium dodecyl sulfate-gel electrophoresis and studies on their subunit association.

The HLA-linked B cell alloantigen (p29,34) is composed of two subunits of 29,000 (p29) and 34,000 (p34) molecular weight. The partially purified HLA-linked B cell alloantigen was purified by a final step of preparative sodium dodecyl sulfate-gel electrophoresis. An antiserum was prepared against p29,34 which specifically lysed B lymphocytes. In sodium dodecyl sulfate at 21 degrees, p29 and p34 remained noncovalently associated and retained immunologic activity; subunit dissociation at higher temperatures correlated with loss of immunologic activity. Although the pI values of p29 and p34 are 6.1 and 5.2, respectively, the subunits co-electrofocus under nondenaturing conditions. In addition, cross-linking studies showed the B cell antigen has a (p29)1(p34)1 subunit structure.

Antigen-Antibody Reactions↗
PubMedDate not supplied

Clinical pharmacokinetics of disopyramide.

Disopyramide is an antiarrhythmic agent with proven efficacy in the management of atrial and ventricular arrhythmias. The drug is well absorbed and undergoes virtually no first-pass metabolism. Peak concentrations are achieved approximately 0.5 to 3.0 hours after a dose. Absorption is reduced and slightly slowed in patients with acute myocardial infarction. Disopyramide is excreted as unchanged drug (two-thirds) or as the metabolite mono-N-desisopropyldisopyramide, with elimination via both renal and biliary routes. Elimination half-life is approximately 7 hours in normal subjects and patients, but is prolonged in patients with renal insufficiency (creatinine clearance less than 60 ml/min). Disopyramide exhibits complex protein binding. It is bound to alpha 1-acid glycoprotein (AAG), an acute phase reactant, and binds in a concentration-dependent (saturable) manner. The unbound fraction is reduced in the presence of elevated concentrations of AAG, as are found in acute myocardial infarction and in some chronic haemodialysis patients and renal transplant recipients. Free disopyramide concentrations are low relative to total concentration in these patients. Because the pharmacological effects of disopyramide are determined by unbound drug, changes in the unbound fraction could make total disopyramide concentrations misleading as a guide to therapy. Changes in protein binding do not, however, alter free disopyramide or metabolite concentrations, both of which are dependent only on dosage and intrinsic clearance. Free drug concentration measurement could potentially improve therapeutic monitoring, but is as yet of unproven clinical value. Disopyramide is cleared more rapidly in children than in adults, and therefore children require higher dosages to attain therapeutic concentrations.

Aged↗