[Serum rifampicin concentrations by means of different assay methods and their critical estimation]

Determination of serum rifampicin (RFP) after dose of the drug is often requested not only for the clinical criteria on its use, but also for the check of its adverse reactions. In comparative examination on each clinical use of 2 kinds of RFP commercial products: Rifadin and Aptesin, the authors had a chance of simultaneous determination of serum RFP by means of 3 different assay methods: solvent extraction method (SE), biological activity method (BA) and liquid-chromatography method (LC). Ten healthy male volunteers and 19 hospital patients (14 males and 5 females) with lung tuberculosis cooperated for this investigations. RFP blood samples were taken serially after oral administration of 450 mg RFP, at 1, 2, 3, 4, 6, 8, 12 and 24 hours in the volunteers, and at 2 and 4 hours in the patients. The serum RFP concentrations determined by the present methods showed generally a good correlation between each other, but there was a considerable difference in their quantity. The highest determinations were presented by the SE, which was devised as total assay method determining desacetyl RFP and 3-formyl rifamycin SV besides free RFP. The lowest determinations were brought about by the LC, which was devised fundamentally for the assay of free RFP. Thus the difference between both determinations by SE and LC was caused by RFP metabolites. This explanation was further proved by the fact that the difference rate, namely (SE-LC)/SE, increased clearly with the lapse of time, and could be used as an index of serial pattern of RFP metabolism. The serum determinations by BA appeared to be useful to monitor clinical efficacy of the drug, but seemed to be out of the absolute estimation. Incidentally the determination by BA was always ranked between both determinations by SE and LC figures. The detailed analysis of two examinations at ten-day intervals in the same volunteers revealed that the RFP determinations by SE appeared to show much better reproducibility than those by BA and LC. By the present assay methods, nearly no difference was demonstrated in the blood level of 2 RFP products. Some attensions were called to the practical estimation of the serum RFP concentrations: Clear individual differences were found in the serum RFP concentrations after dose of the drug, and appeared to become clearer in the stage of its continuous administrations. Above all, it was noteworthy that the individual difference in the first dose of RFP was found to be decided by the grade of absorption within 2 hours after the dose.(ABSTRACT TRUNCATED AT 400 WORDS)