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Biomedical subjects

C M Macdonald

Publications and source records attributed to C M Macdonald.

9 recordsLinked to original sources
PubMed1989

Metabolism and pharmacokinetics of 14C-pentoxifylline in healthy volunteers.

The metabolism and pharmacokinetics of 14C-pentoxifylline (Trental) have been studied in three healthy male volunteers after oral administration of 200 mg (50 microCi). The radiolabelled drug was rapidly absorbed and by 6 h 89.1 +/- 2.4% of the 14C material was excreted in the urine. The dosed 14C material (96.9 +/- 2.2%) was recovered in excreta by 24 h with 93.3 +/- 2.3% in the urine 3.0 +/- 0.2% in the faeces. Peak plasma levels of radioactivity (4.1-6.2 micrograms eq ml-1) occurred 0.25-0.75 h after administration. This radioactivity decayed in a biexponential fashion with an initial half-life of 1.01 +/- 0.13 h and a terminal half-life of 36.06 +/- 16.94 h. The peak plasma levels (0.48-2.25 micrograms ml-1) of parent drug, as measured using a specific gas chromatographic assay also occurred at 0.25-0.75 h and subsequently decayed extremely rapidly with an initial half-life of 0.18 +/- 0.15 h and terminal half-life of 0.76 +/- 0.44 h. Urinary 14C-labelled metabolites were separated by semi-preparative high performance liquid chromatography and characterised by mass spectrometry and by comparison with authentic synthetic compounds. Of the dosed 14C-pentoxifylline, greater than 90% could be identified as characterised metabolites in urine.

Biotransformation↗
PubMed1984

Disposition of cefotaxime in rat, dog and man.

The excretory pathway for the elimination of 14C-cefotaxime (14C-HR 756) was found to be the same for rat, dog and man with elimination into the urine being the most important route, accounting for greater than 80% of the dosed radioactivity. The amounts of unchanged cefotaxime eliminated in the urine ranged from 20-32% in rat and dog to 56% in man. The major metabolite in each species was the microbiologically active desacetyl cefotaxime, which was present in both plasma and urine. Two further metabolites, recently identified as the stereoisomeric forms of the opened beta-lactam ring form of desacetyl cefotaxime lactone were also found in the urine of dog and man.

Adult↗
PubMed1984

Cefotaxime: sites and pathway of metabolic conversion.

This paper examines the metabolism of 14C-cefotaxime (14C-HR 756) in the rat and attempts to identify the metabolic events in this and other species. In rat desacetyl cefotaxime is usually the major excretion product and sole metabolite of cefotaxime. However, when renal elimination of this metabolite is prevented by bilateral nephrectomy, two further metabolites, the stereoisomeric opened beta-lactam ring forms of desacetyl cefotaxime lactone, are also produced. These metabolites are found in the urine of man and dogs dosed with cefotaxime. It is suggested that generation of these metabolites is dependent on formation of the lactone form of the desacetyl metabolite. Evidence is also presented showing that these metabolic conversions occur in the liver.

Animals↗
PubMed1980

An isolated rat lung perfusion system for use in tobacco smoke studies.

An isolated rat lung perfusion system has been developed for use in tobacco smoke studies. The lungs are ventilated by means of subatmospheric (negative) pressure produced through operation of an artificial thorax. The system enables standard respiratory conditions to be employed and so eliminates variations in animal breathing characteristics. The various tests of viability which have been carried out have shown that the preparations are viable for periods of at least 1 hr. It was also demonstrated that transfer of 14C-nicotine from smoke to perfusate was rapid and linear over the period of smoke exposure and that first-pass metabolism of nicotine was of little significance.

Absorption↗