PubMed Health⌕ Search

Biomedical subjects

S R Bushby

Publications and source records attributed to S R Bushby.

At least 19 recordsLinked to original sources
PubMed1981

2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 5. 3',5'-Dimethoxy-4'-substituted-benzyl analogues of trimethoprim.

Forty trimethoprim analogues in which the para substituent in the benzene ring was varied were prepared for antibacterial evaluation. All were very potent inhibitors of Escherichia coli dihydrofolate reductase. The similarity of their inhibitory activities strongly suggested that the side chains beyond the first two atoms were not in contact with the enzyme. However, among 38 ether derivatives which varied widely in their bulk and lipophilicity, very few approached trimethoprim in their broad-spectrum in vitro antibacterial activity. The 4'-methyl and 4'-ethyl analogues and the allyloxy and gamma-chloropropoxy ethers had activities fairly close to that of trimethoprim. The two ethers were chosen for further evaluation in vivo. Neither compound quite matched trimethoprim in efficacy in mice, and their half-lives, as well as that of the beta-methoxyethoxy analogue, were found to be shorter in dogs.

Animals↗
PubMed1981

Pharmacokinetics of trimethoprim and sulfadiazine in the dog: urine concentrations after oral administration.

Serial blood samples were obtained from 12 healthy adult dogs given equivalent subcutaneous and oral doses of the antibacterial combination, trimethoprim-sulfadiazine (1:5). By using a 1-compartment open model, pharmacokinetic parameters for both drugs were estimated from the mean serum concentration data after oral administration. Trimethoprim and sulfadiazine were rapidly absorbed, reaching maximum concentrations in 1 and 4 hours with serum elimination half-lives of 2.5 and 9.9 hours, respectively. After a single oral dose (30 mg/kg, combined ingredients) was given, both drugs were present in urine for up to 24 hours at concentrations exceeding the minimum inhibitory concentrations for common pathogenic bacteria.

Administration, Oral↗
PubMed1975

Identification of Harper-Cawston factor as thymidine phosphorylase and removal from media of substances interfering with susceptibility testing to sulfonamides and diaminopyrimidines.

Rich media support the growth of bacteria in the presence of concentrations of sulfonamides and diaminopyrimidines that are highly inhibitory when the organisms are grown on minimal media. Many such rich media can be made more suitable for susceptibility testing by the incorporation of lysed horse blood. Harper and Cawston characterized the active substance, Harper-Cawston factor (HCF), and later studies indicated it to be a protein. It has now been identified as thymidine phosphorylase. The identification follows from the identical purification pattern of HCF and thymidine phosphorylase activities from horse blood to a high degree of purity. Blood of goats, sheep, oxen, geese, chickens, cows, dogs, rats, and humans had neither biological activity. The identification of HCF as thymidine phosphorylase is consistent with the earlier findings of Koch and Burchall (1971) that most of the interfering effects of rich media could be accounted for by their thymidine contents, and that thymidine is much more active in this respect than is thymine.

Animals↗
PubMed1975

Diffusion of trimethoprim and sulfamethoxazole from susceptibility disks into agar medium.

The standard practice of using a single susceptibility disk for the antimicrobial combination Septra (trimethoprim/sulfamethoxazole) has been further justified by a direct measurement of the diffusion rates of each compound through agar medium. [(14)C]trimethoprim and [(35)S]sulfamethoxazole, singly and in combination, were applied to blank susceptibility disks which were incubated on 4-inch (10.16-cm) agar plates (Mueller-Hinton medium) at 37 C. The migration of each compound from the disk and diffusion through agar were measured with time by determining the radioactivity in concentric zones extending from the origin. The two compounds diffuse with similar rates, maintaining approximately a 1:20 concentration ratio which is approximately the ratio of trimethoprim to sulfamethoxazole observed in plasma during treatment. The diffusion rate is independent of the presence of the other compound; greater than 95% of the radioactivity is transferred from the disk to the agar in 24 h.

Agar↗