Serum concentrations and antituberculosis activity of thiacetazone.
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Biomedical subjects
Publications and source records attributed to D A Mitchison.
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Two methods for the assay of rifampicin in serum are described. The first is a conventional plate diffusion method, measuring concentrations down to 0.02 mug/ml, and the second a chemical extraction followed by measurement of the inhibition of uptake of (14)C-uridine by Staphylococcus aureus, which estimates in the range of 0.02 to 0.001 mug/ml. The methods were used to measure serum concentrations in man following doses of about 1050 mg and 75 mg rifampicin.
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Direct culture on Lowenstein-Jensen slopes and on three media made selective for tubercle bacilli by the addition of four antibacterial agents was compared with guinea-pig inoculation on 490 tissue specimens. Tubercle bacilli were obtained from 15 specimens by culture and 14 by guinea-pig inoculation; only one specimen was positive by guinea-pig and not by culture. The most efficient culture medium was a selective 7H11 slope. Routine guinea-pig inoculation has been replaced by a wider range of culture procedures.
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Sulphadimidine acetylation studies were undertaken in 103 patients, 52 of whom had been classified as slow and 51 as rapid inactivators of isoniazid by a standard microbiological assay method. Each patient received sulphadimidine by mouth in a dose of 44 mg./kg. body weight, and free and total sulphadimidine were estimated in blood and urine collected at six hours. The findings suggest that patients may be classified as slow inactivators of isoniazid if the proportion of acetylated sulphadimidine (total minus free) is (a) less than 25% in blood or (b) less than 70% in urine. The sulphadimidine test is easy to perform and the result is available the same day; urine specimens for the test can be stored at room temperature for over a week without any loss of drug.