P. A. Cossum
University of Tasmania
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Journal of Pharmacy and Pharmacology | 1980
Michael S. Roberts; P. A. Cossum; A. J. Galbraith; G. W. Boyd
The availability of nitroglycerin from solutions infused from Viaflex plastic infusion bags or glass infusion bottles through Buretrol plastic giving sets has been examined. Each of the individual components of the infusion bag/giving set system (i.e. infusion bag, burette and infusion tubing) sorbed nitroglycerin to a significant extent. It was found that the extent and rate of nitroglycerin disappearance from solutions stored in each of the components were in the rank order: tubing > burette > infusion bag. The disappearance kinetics of nitroglycerin from solutions stored in each component was more accurately described by a ‘diffusion’ model than by the ‘two compartment kinetic’ model reported previously. The dimensions of the components and the volume of solution used were determinants of the rate and extent of nitroglycerin disappearance. In simulated infusions of nitroglycerin through plastic infusion bag (or glass bottle)/giving set system the flow rate of solution through the plastic infusion tubing affected the concentration of nitroglycerin in the effluent and the extent of sorption by the components of the infusion delivery system. The loss of nitroglycerin in these studies could be accounted for solely by the sorption of nitroglycerin by the plastic components of the infusion bag/giving set system.
European Journal of Clinical Pharmacology | 1984
Michael S. Roberts; L. J. McLeod; P. A. Cossum; J. H. Vial
SummaryThe extent to which a controlled release acetylsalicylic acid (ASA) formulation inhibited platelet function has been evaluated in single and chronic dosing studies. In the single dose study, the platelet inhibitory effect of the controlled release formulation was compared with that of an equivalent dose of soluble ASA and an equimolar dose of sodium salicylate (SA). In the chronic dosing study, ASA dose-response curves for platelet function, including cyclooxygenase activity, were determined for various doses (20–1300 mg) of the controlled release (enteric coated pellets) ASA formulation taken by volunteers daily for one week. Platelet function was assessed by the degree of inhibition of aggregation for several aggregating agents, and the degree of inhibition of activity of platelet cyclooxygenase quantified by the estimation of malondialdehyde (MDA) production. Plasma ASA and SA concentrations were also determined in each study. The controlled release product inhibited platelet function to the same extent as an equimolar dose of soluble ASA, but did so with much lower and sometimes undetectable peak systemic plasma ASA concentrations. SA, the direct metabolite of aspirin, did not have any effect on platelet function. The ASA dose-platelet function response curves obtained from chronic dosing with the controlled release formulation appeared to be similar to those reported previously for the soluble product. The inhibition of platelet function appeared to be unrelated to plasma ASA concentrations.
European Journal of Clinical Pharmacology | 1981
P. A. Cossum; Michael S. Roberts
SummaryThe loss of isosorbide dinitrate from aqueous solutions stored in plastic infusion bags and/or infused through plastic giving sets was investigated. During simulated infusions, the loss of isosorbide dinitrate was found to be flow-rate dependent. The clinical and pharmacokinetic significance of this loss is discussed. Infusion of isosorbide dinitrate from a glass syringe through high density polyethylene tubing overcame the loss associated with its adinistration via plastic infusion bags and intravenous giving sets. This method was also applied successfully to minimise the previously reported loss of diazepam and chlormethiazole during infusions.
European Journal of Clinical Pharmacology | 1985
P. A. Cossum; Michael S. Roberts
SummaryThe disposition in vitro of nitroglycerin (GTN) and its metabolites in erythrocyte suspensions, plasma and blood has been studied using labelled (3H) and unlabelled GTN and GTN metabolites separated by HPLC. GTN was rapidly metabolised (t1/2 3 min) to dinitro-metabolites and subsequently to the mononitronitrates in erythrocyte suspensions containing a therapeutic concentration of GTN (0.8–10 ng/ml). The metabolism of GTN and its dinitro-metabolites was concentration dependent. GTN and its dinitro-metabolites were plasma protein bound (11–60%). They had an apparent erythrocyte-plasma partition coefficient in the range 0.6 to 0.9. The metabolism of GTN by erythrocytes was partially inhibited by the presence of the dinitro-metabolites of GTN. The metabolism of GTN in blood samples collected from patients could be stopped by adding the collected blood to chilled tubes containing the enzyme inhibitor iodoacetamide.
International Journal of Pharmaceutics | 1983
Michael S. Roberts; P. A. Cossum; Elizabeth A. Kowaluk; Alan E. Polack
Abstract The organic nitrate most recently introduced for clinical use (isosorbide-5-mono-nitrate) is not lost by sorption into the plastics of infusion systems. Other organic nitrates with 2 or 3 nitrate groups are lost by sorption into the plastic matrix of infusion systems at ambient temperature. At higher temperatures, evaporation of nitroglycerin and ethylene glycol dinitrate from the plastic to the atmosphere also contributes to the total loss of these compounds. The temperature-dependent sorption of all 3 organic nitrates by the plastic infusion bags is accounted for by changes in the diffusion coefficients of the organic nitrates in the plastic matrix, the plastic-water partition coefficients being independent of temperature. The extent of loss of the 3 organic nitrates corresponds to the rank order of their plastic (and organic solvent)-water partition coefficients i.e. nitroglycerin > isosorbide dinitrate > ethylene glycol dinitrate. It is suggested that the chloroform-water partition coefficient may be a useful parameter for the prediction of the interaction of a drug with polyvinyl chloride infusion systems.
Journal of Pharmacy and Pharmacology | 1985
P. A. Cossum; Michael S. Roberts
The metabolism of nitroglycerin in sheep tissue homogenates has been examined using tritiated nitroglycerin and a HPLC separation procedure. Nitroglycerin was metabolized by liver, lung, muscle, arterial and venous tissue to its dinitrometabolites and subsequently to mononitroglycerin. Addition of the dinitrometabolites substantially inhibited the degradation of nitroglycerin in all tissue homogenates.
Journal of Pharmacology and Experimental Therapeutics | 1986
P. A. Cossum; Michael S. Roberts; Ac Yong; D Kilpatrick
Journal of Pharmaceutical Sciences | 1986
P. A. Cossum; Michael S. Roberts; D Kilpatrick; Ac Yong
Scandinavian Journal of Haematology | 2009
L. J. McLeod; Michael S. Roberts; P. A. Cossum; J. H. Vial
The Medical Journal of Australia | 1981
Michael S. Roberts; P. A. Cossum; Elizabeth A. Kowaluk; Alan E. Polack; Flukes Wk