McLachlan A J, Tett S E, Cutler D J, Day R O
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, Sydney, Australia.
Chirality. 1994;6(4):360-4. doi: 10.1002/chir.530060421.
The disposition of hydroxychloroquine enantiomers has been investigated in nine patients with rheumatoid arthritis following administration of a single dose of the racemate. Blood concentrations of (-)-(R)-hydroxychloroquine exceed those of (+)-(S)-hydroxychloroquine following both an oral and intravenous dose of the racemate. Maximum blood concentrations of (-)-(R)-hydroxychloroquine were higher than (+)-(S)-hydroxychloroquine after oral dosing (121 +/- 56 and 99 +/- 42 ng/ml, respectively, P = 0.009). The time to maximum concentration and the absorption half-life, calculated using deconvolution techniques, were similar for both enantiomers. The fractions of the dose of each enantiomer absorbed were similar, 0.74 and 0.77 for (-)-(R)- and (+)-(S)-hydroxychloroquine, respectively (P = 0.77). The data suggest that absorption of hydroxychloroquine is not enantioselective. The stereoselective disposition of hydroxychloroquine appears to be due to enantioselective metabolism and renal clearance, rather than stereoselectivity in absorption and distribution.
在9名类风湿性关节炎患者单次服用消旋体后，对羟基氯喹对映体的处置情况进行了研究。口服和静脉注射消旋体后，（-）-（R）-羟基氯喹的血药浓度均超过（+）-（S）-羟基氯喹。口服给药后，（-）-（R）-羟基氯喹的最大血药浓度高于（+）-（S）-羟基氯喹（分别为121±56和99±42 ng/ml，P = 0.009）。使用反卷积技术计算，两种对映体达到最大浓度的时间和吸收半衰期相似。每种对映体吸收的剂量分数相似，（-）-（R）-和（+）-（S）-羟基氯喹分别为0.74和0.77（P = 0.77）。数据表明，羟基氯喹的吸收没有对映体选择性。羟基氯喹的立体选择性处置似乎是由于对映体选择性代谢和肾脏清除，而不是吸收和分布中的立体选择性。
