INTERACTIONS AMONG PRIMAQUINE, MALARIA INFECTION AND OTHER ANTIMALARIALS IN THAI SUBJECTS
INTERACTIONS AMONG PRIMAQUINE, MALARIA INFECTION AND OTHER ANTIMALARIALS IN THAI SUBJECTS
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DOI：
10.1111/j.1365-2125.1993.tb05685.x
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发表时间：
1993-02-01
影响因子：
3.4
通讯作者：
WHITE, NJ
中科院分区：
文献类型：
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作者：
EDWARDS, G;MCGRATH, CS;WHITE, NJ
1泰籍健康成人单剂量口服甲氟喹(10 mg·kg~(-1))前后的药代动力学研究表明，伯喹在健康成人体内吸收迅速，在2(1~4)h内达到峰值血药浓度(中位数和极差)167(113~532)µg L~(-1)，随后浓度迅速下降，表观半衰期为6.1(1.7~16.1h)h，口服清除量(CLPO)为33.1(17.6~49.3)h~(-1)。甲氟喹对上述参数均无显著影响[C(Max)229(114-503)MUG L-1；(T)max 3(2-4)h；T1/2，Z3.9(1.7-13.5)h；CLPO 34.0(21.7-49)]。3伯氨喹的羧酸代谢产物在6(3-16)h达到最大浓度(中位数和极差)[C(Max)1035g L-1，t(Max)8(2-24)h，AUC(0，24 h)为12737(6837-27388)g L-1h；AUC(0，24)13471(2132-17863)g L-1h]。4奎宁(10 mg盐·kg~(-1)P.O.)治疗恶性疟疾的效果伯喹(45 mg碱基P.O.)的药代动力学研究在感染恶性疟疾期间和之后对泰国成年患者进行了调查。急性恶性疟疾与伯氨喹的口服清除量(L h-1；中位数和范围)从21.3%(15.9-73.0)减少到19.4%(9.3-24.7)有统计学意义的显著(P<；0.05)。5与奎宁和伯氨喹联合使用后，伯氨喹的羧酸代谢产物(中位数和范围)的曲线下面积(Auc(O，24 h)；MUg L-1h)显著更大(P<；0.05)。5882)。
1 The pharmacokinetics of rac-primaquine (45 mg base) and its principal plasma metabolite, carboxyprimaquine have been investigated in healthy Thai adults prior to and following a single oral dose of mefloquine (10 mg kg-1).2 Primaquine was rapidly absorbed, attaining peak plasma concentrations (median and range) of 167 (113-532) mug l-1 in 2 (1-4) h. Thereafter, concentrations declined rapidly with an apparent terminal half-life of 6.1 (1.7-16.1) h and an oral clearance (CLpo) of 33.1 (17.6-49.3) l h-1. Administration of mefloquine had no effect on the values of any of these parameters at the 5% level of significance [C(max) 229 (114-503) mug l-1; (t)max 3 (2-4) h; t1/2,Z 3.9 (1.7-13.5) h; CLpo 34.0 (21.7-49. 0) l h-1].3 The carboxylic acid metabolite of primaquine achieved maximum concentrations (median and range) of 890 (553-3634) mug l-1 at 6 (3-16) h. Thereafter, plasma concentrations of carboxyprimaquine declined to 346 (99-918) mug l-1 at 24 h. AUC (0,24 h) was 12737 (6837-27388) mug l-1 h. Administration of mefloquine had no effect on the plasma concentrations of this metabolite [C(max) 1035 (174-3015) mug l-1; t(max) 8 (2-24) h; AUC(0,24) 13471 (2132-17863) mug l-1 h].4 The effect of falciparum malaria and treatment with quinine (10 mg salt kg-1 p.o.) on the pharmacokinetics of primaquine (45 mg base p.o.) has been investigated in adult Thai patients during and after infection with falciparum malaria. Acute falciparum malaria was associated with a statistically significant (P < 0.05) reduction in oral clearance (l h-1; median and range) of primaquine from 21.3 (15.9-73.0) to 19.4 (9.3-24.7).5 The area under the curve (AUC(O, 24 h); mug l-1 h) for the carboxylic acid metabolite of primaquine (median and range) was significantly greater (P < 0.05) following the administration of primaquine alone (7533; 4876-18545) relative to the combination of quinine and primaquine (3831; 2144;5882).