McColl K E, Thompson G G, el Omar E, Moore M R, Park B K, Brodie M J
Br J Clin Pharmacol. 1987 May;23(5):553-9. doi: 10.1111/j.1365-2125.1987.tb03091.x.
Haem and bilirubin metabolism was studied in seven healthy volunteers during 4 weeks treatment with rifampicin 600 mg at night. The serum unconjugated bilirubin concentration increased 2-3 fold in the first 24 h of treatment (P less than 0.01) and subsequently fell to below pretreatment values (P less than 0.05) during the third and fourth weeks of rifampicin therapy. In each subject, the activity in leucocytes of delta-aminolaevulinic acid (ALA) synthase increased and that of protoporphyrinogen (proto) oxidase decreased during the first week of therapy. The mean ALA synthase activity was most markedly increased on day 4 being seven-fold its pretreatment value (P less than 0.01), and the mean proto oxidase activity most depressed on day 2 at 50% its pretreatment value (P less than 0.02). There was increased urinary excretion of porphobilinogen (PBG) during the first week of therapy and increased excretion of porphyrins and PBG during the third week of treatment. The increase in ALA synthase activity and haem precursor excretion can be explained by the combination of increased haem demand for haemoprotein induction and partial block in haem synthesis due to reduced proto oxidase activity.
在7名健康志愿者夜间服用600mg利福平治疗4周期间，对其血红素和胆红素代谢进行了研究。治疗的最初24小时内，血清非结合胆红素浓度增加了2 - 3倍（P<0.01），随后在利福平治疗的第三和第四周降至治疗前值以下（P<0.05）。在治疗的第一周，每个受试者白细胞中δ-氨基乙酰丙酸（ALA）合酶的活性增加，而原卟啉原（proto）氧化酶的活性降低。平均ALA合酶活性在第4天增加最为明显，是其治疗前值的7倍（P<0.01），平均原卟啉氧化酶活性在第2天降低最为显著，为其治疗前值的50%（P<0.02）。治疗第一周尿卟胆原（PBG）排泄增加，治疗第三周卟啉和PBG排泄增加。ALA合酶活性和血红素前体排泄的增加可以通过对血红蛋白诱导的血红素需求增加以及由于原卟啉氧化酶活性降低导致血红素合成部分受阻来解释。
