Peters J H, Murray J F, Gordon G R, Levy L, Russell D A, Scott G C, Vincin D R, Shepard C C
Am J Trop Med Hyg. 1977 Jan;26(1):127-36. doi: 10.4269/ajtmh.1977.26.127.
In 22 lepromatous Filipino patients receiving their first injection of 225 mg acedapsone (DADDS), dapsone (DDS), and monoacetyl DDS (MADDS) were present in plasma in approximately equal quantities. Peak levels of parent drug, DDS, and MADDS occurred between 22 and 35 days. The half-times of disappearance (T1/2) from plasma were 43 days for DDS and MADDS and 46 days for DADDS. Acetylator phenotyping with sulfamethazine (SMZ) and DDS showed that 17 patients were rapid and 5 patients were slow acetylators. Correlations between acetylation of SMZ and DDS after DDS and of acetylation of DDS after DDS and DADDS were highly significant. However, acetylation of DDS after DADDS did not differentiate the patients into acetylator phenotypes. The T1/2 of DDS after DDS in the patients was directly related to the minimum levels of DDS at 77 days after DADDS treatment. These minimum levels were 8-fold higher than the minimum inhibitory concentration (MIC) of DDS for Mycobacterium leprae in mice and rats, but not all patients responded satisfactorily. No relationship could be demonstrated between the bacteriologic response and any of the pharmacologic parameters examined in these Filipino patients. In a companion study, minimum levels of DADDS, MADDS, and DDS were determined in 447 leprosy patients of all disease types from the Karimui District of Papua New Guinea who had been receiving 225 mg DADDS every 70 to 80 days for the past 5 years. All patients exhibited DDS levels above the MIC of DDS for M. leprae, no significant differences in plasma sulfone levels were found among disease types, no relationship between rate of healing in paucibacillary patients and sulfone levels were found, and type of response in multibacillary patients and sulfone levels were unrelated. No substantial accumulation of the sulfones in the Karimui patients receiving continuous therapy with DADDS for 5 years was indicated from a comparison with the levels in the Filipino patients following a single injection of DADDS.
在22例接受首次225毫克醋氨苯砜（DADDS）注射的菲律宾瘤型麻风患者中，血浆中氨苯砜（DDS）和单乙酰氨苯砜（MADDS）的含量大致相等。母体药物、DDS和MADDS的峰值水平出现在22至35天之间。DDS和MADDS从血浆中消失的半衰期（T1/2）为43天，DADDS为46天。用磺胺二甲嘧啶（SMZ）和DDS进行乙酰化表型分析表明，17例患者为快速乙酰化者，5例患者为慢速乙酰化者。DDS后SMZ与DDS的乙酰化之间以及DDS和DADDS后DDS的乙酰化之间的相关性非常显著。然而，DADDS后DDS的乙酰化并不能将患者区分为乙酰化表型。患者中DDS后DDS的T1/2与DADDS治疗77天后DDS的最低水平直接相关。这些最低水平比小鼠和大鼠中麻风分枝杆菌对DDS的最低抑菌浓度（MIC）高8倍，但并非所有患者的反应都令人满意。在这些菲律宾患者中，细菌学反应与所检测的任何药理学参数之间均未显示出相关性。在一项配套研究中，对巴布亚新几内亚卡里穆伊地区过去5年中每70至80天接受225毫克DADDS治疗的447例所有疾病类型的麻风患者，测定了DADDS、MADDS和DDS的最低水平。所有患者的DDS水平均高于麻风分枝杆菌对DDS的MIC，疾病类型之间血浆砜水平无显著差异，少菌型患者的愈合速度与砜水平之间未发现相关性，多菌型患者的反应类型与砜水平无关。与单次注射DADDS后的菲律宾患者水平相比，未表明接受DADDS持续治疗5年的卡里穆伊患者中有砜的大量蓄积。
