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Biomedical subjects

R H Nimmo-Smith

Publications and source records attributed to R H Nimmo-Smith.

9 recordsLinked to original sources

Interaction between warfarin and sulphamethoxazole.

A patient is described in whom there was strong circumstantial evidence of an interaction between warfarin and co-trimaxazole. To test the validity of this hypothesis a series of in vitro and in vivo human studies were untaken. The results indicate that interaction may occur in which the sulphamethoxazole moiety of co-trimoxazole displaces warfarin from its binding sites on plasma albumin. Nevertheless, this interaction occurs only at high plasma levels of warfarin and is most likely to be clinically significant only in patients receiving high doses of warfarin who have low plasma albumin concentrations. These studies indicate that the use of co-trimoxazole is not contra-indicated in patients receiving warfarin therapy, but care should be exercised, especially in patients with high plasma warfarin:albumin ratios.

Adult↗

Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode.

1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of substrate disappearance or product formation. 4. The practical applications of the gold electrode to drug metabolism studies are discussed.

Animals↗

Effects of Corynebacterium parvum vaccine on drug metabolism in the mouse.

Mice of the CBA strain were given a single intraperitoneal injection of C. parvum vaccine at 50 mg/m2. There followed a progressive increase in liver weight and in the duration of hexobarbitone sleeping time, accompanied by a marked decrease in liver microsomal protein and in cytochrome P-450/mg microsomal protein. That is to say, content of cytochrome P-450 was reduced out of proportion to the apparent loss of endoplasmic reticulum. These changes were paralleled by decreases in microsomal O-demethylation of p-nitroanisole and glucuronide formation with o-aminophenol measured in vitro; they were most marked at 13-14 days after dosing; they then slowly returned to control levels which they reached 20-30 days later. Changes in the dose of vaccine showed that the increase in liver weight and in hexobarbitone sleeping time were significant at 3.5 mg/m2, but that the decrease in the activities measured in vitro were not significant below 35 mg/m2.

Animals↗