書誌事項
- タイトル別名
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- Studies of the serum rifampicin concentration.
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抄録
A high performance liquid chromatography (HPLC) technique permits the determination of rifampicin (RFP) and 2.5-desacetyl RFP (DES-RFP) in human serum. It can be used to determine the serum concentration of RFP in patients. The purpose of this study is to determine the relationship between the clinical efficacy of RFP and its level of serum concentration. We measured the serum concentration of RFP in 41 tuberculous patients admitted to 6 National Sanatoria. All of them were previously untreated, and culturepositive. These cases were bacteriologically and radiologically followed up for at least 6 months from the beginning of treatment. RFP was administered at a single dose of 0.45g orally in the fasting state. Blood samples were taken at 0, 2, 4, and 6 hours after the initial administration. As it was well established that repeated daily administration of RFP results in a decrease of serum concentration, we measured the serum concentration of RFP at 1, 2, 3, and 6 months after the initial administration during the treatment. We used HPLC for the quanititative analysis of RFP and DES-RFP, on the method of assay was as follows:<BR>Instruments: a Model ALC/GPC 204 high performance liquid chromatograph (Waters Assoc.)<BR>Column: a stainless-steel tube (30×4mm i. d.) filled with u-Bondapack C18 (Waters Assoc.)<BR>Mobile phase: 38%CH3 CN/0.01M CH3 COONa (ajusted to pH7.0 with CH3COOH)<BR>Flow rate: 1.0ml/min<BR>Detection: a Model 440 fixed-wavelength (340nm) UV absorbance detector (Waters Assoc.)<BR>Assay procedure: To 50μl of plasma in 1-ml tube, 200μ; of methanol containing 500pg/μ1 p-nitrophenol, internal standard, is added. The tube is stoppered and mechanically shaken, then centrifuged for 5 min. at 3, 000 rpm. A 100-μl portion of supernatant is injected into the chromatographic column. The concentration of RFP and DES-RFP are calculated by measuring the peak heights of chromatogram.<BR>Calibration: Calibration samples are prepared by measuring 50μl of standard RFP (150, 100, 80, 50, 30, 10ng) and DES-RFP (50, 40, 30, 20, 10, 5ng) methanol solutions into 1-ml t ubes. Methanol is evaporated under nitrogen, and the compounds are redissolved in 200μ of methanol containing 500pg/μl p-nitrophenol, internal standard and 50μl of plasma is added. The assay is done as described.<BR>The following results were obtained<BR>1) The mean peak serum concentration of RFP and DES-RFP on the first administration was 5.5±3.20μg/ml at 2 hours after the administration and 0.97±0.71μg/ml at 4 hours, respectively.<BR>2) The serum peak value of RFP and DES-RFP decreased after 1 month starting administrAtion and there after it kart the same level during treatment.<BR>3) We could neither find any relationship between the clinical prognosis and RFP serum levels nor the relation between the side effect and the serum levels of DES-RFP.
収録刊行物
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- 結核
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結核 61 (8), 425-433, 1986
一般社団法人 日本結核病学会