Biomedical subjects
Publications and source records attributed to P S Collier.
In a randomised crossover study in volunteers plasma midazolam levels were estimated for 24 h following 15 mg by mouth, either preceded by no medication or following 24 h therapy with ranitidine. Administration of the H2-receptor blocker significantly increased bioavailability of the benzodiazepine and resulted in higher plasma levels for the first 6 h after taking midazolam. This was accompanied by a greater soporific effect.
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1 The bioavailabilty of phenytoin sodium (Epanutin both alone and in combination with activated dimethicone and Asilone (a proprietary antacid preparation containing activated dimethicone) was examined in six healthy male volunteers. 2 The bioavailability of phenytoin when given concomitantly with Asilone was decreased in five of six volunteer subjects (by greater than 30% in three subjects) although this decrease was not shown to be statistically significant. 3 Dimethicone, which has been shown to decrease phenytoin absorption in vitro did not affect phenytoin bioavailability in vivo. 4 It is recommended that when treating patients stabilised on phenytoin one should exercise caution with concomitant phenytoin and antacid therapy to guard against possible changed drug absorption.
An in vitro study indicated that certain antacids and adsorbents may decrease the oral availability of th two widely used antimalarial agents chloroquine and pyrimethamine. To determine if this data was applicable to the clinical (in vivo) situation, plasma levels of one of the antimalarial agents (chloroquine) were followed in six Negro--Arab volunteers both when given alone and when taken with separate doses of two of the implicated interactants (magnesium trisilicate and kaolin). This in vivo work confirmed the in vitro findings; chloroquine area under the plasma concentration-time curve data were decreased by both magnesium trisilicate (18.2%) and kaolin (28.6%). Similar results could be expected for pyrimethamine. It is suggested therefore, to avoid loss of drug, that the antimalarials should not be taken with gastrointestinal medications of this type or that their administration should be separated by at least 4 h to reduce the risk of them interacting in the gut, thus preventing drug adsorption to the antacids/adsorbents, and loss of systemic availability.
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A study was made of the effect of 4 constituents of antacid preparations on the absorption of the coumarin derivate warfarin sodium using an in vitro experimental model. The constituents tested were activated dimethiocone (a silicone) magnesium trisilicate, bismuth carbonate and the adsorbant, kaolin. Slight decreased intestinal absorption was shown by magnesium trisilicate (19%) and bismuth carbonate (7%), the other 2 components showing no effects.
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The correct use of probability distribution functions is described for the determination of mean residence time (MRT) of drug molecules in the body and is illustrated for two possible two compartment body models. A new method for estimating (MRT) is described, based on the area under the curve measurement for the decay of drug from steady state.
The metabolism of the antiepileptic drug ethosuximide (3-ethyl-3-methylpyrollidine-2,5-dione) (I) in animals and humans is reviewed. Chiral aspects of the metabolism of ethosuximide are discussed. Clarification of the precise nature of the hydroxymetabolites of ethosuximide is presented.
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