Binh Vu Quoc, Chinh Nguyen Trong, Thanh Nguyen Xuan, Cuong Bui Tri, Quang Nguyen Ngoc, Dai Bui, Travers Thomas, Edstein Michael D
Department of Infectious Disease, Central Military Hospital, Hanoi, Vietnam.
Am J Trop Med Hyg. 2009 Nov;81(5):747-53. doi: 10.4269/ajtmh.2009.09-0214.
We evaluated whether sex affects the steady-state pharmacokinetics of the antimalarial drugs, primaquine and doxycycline, in healthy subjects. Seventeen male and 17 female healthy Vietnamese subjects were administered 30 mg (base) of primaquine daily for 14 days. After a 2-week washout period, 14 male and 14 female subjects were administered 100 mg (base) of doxycycline daily for 14 days. Women had significantly higher median values of C(max) (212 versus 122 ng/mL, P< 0.001) and AUC(0-24) (1,909 versus 917 ng . h/mL, P < 0.001) of primaquine compared with men. Other than a longer t(max) in women, no sex-related differences were seen in the pharmacokinetics of doxycycline. The primaquine pharmacokinetic data suggest that women have increased exposure to primaquine, which may put them at increased risk for toxicity when administered the same maintenance dose as men. The similar pharmacokinetics of doxycycline between the two sexes justifies the same maintenance dose.
我们评估了性别是否会影响抗疟药物伯氨喹和多西环素在健康受试者体内的稳态药代动力学。17名健康的越南男性受试者和17名健康的越南女性受试者每天服用30毫克（碱基）伯氨喹，持续14天。经过2周的洗脱期后，14名男性受试者和14名女性受试者每天服用100毫克（碱基）多西环素，持续14天。与男性相比，女性的伯氨喹C(max)中位数显著更高（212对122纳克/毫升，P<0.001），AUC(0 - 24)中位数也显著更高（1909对917纳克·小时/毫升，P < 0.001）。除了女性的t(max)更长外，多西环素的药代动力学未观察到与性别相关的差异。伯氨喹的药代动力学数据表明，女性对伯氨喹的暴露增加，当给予与男性相同的维持剂量时，她们可能面临更高的毒性风险。两性之间多西环素相似的药代动力学证明了相同维持剂量的合理性。
