Pharmacometric assessment of primaquine induced haemolysis in glucose-6-phosphate dehydrogenase deficiency
Pharmacometric assessment of primaquine induced haemolysis in glucose-6-phosphate dehydrogenase deficiency
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葡萄糖-6-磷酸脱氢酶缺乏症中伯氨喹诱导溶血的药理学评估
DOI：
10.1101/2023.02.24.23286398
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Pukrittayakamee S
中科院分区：
文献类型：
--
作者：
Pukrittayakamee S
伯氨喹是一种8-氨基喹啉类抗疟药。它是唯一广泛使用的预防间日疟原虫疟疾复发的治疗方法。在葡萄糖-6-磷酸脱氢酶缺陷（G6 PDd）个体中，8-氨基喹啉类药物引起剂量依赖性溶血。G6 PDd在疟疾流行地区很常见，但通常无法进行检测。因此伯氨喹是underused.MethodsWe进行了一项药物计量学研究，以确定伯氨喹剂量和溶血G6 PDd之间的关系。目的是探索与目前推荐的8周一次方案（0.75 mg/kg，每周一次）相比更短，更安全的伯氨喹根治方案，可能避免G6 PD检测的需要。半合子G6 PDd健康成年泰国和缅甸男性志愿者入住曼谷的热带病医院。在第1部分中，志愿者接受递增剂量伯氨喹方案，每日剂量从7.5 mg增加到45 mg，持续15至20天。第2部分单次给予伯氨喹45 mg。结果第1部分24例，第2部分16例（13例同时参加两项研究）。在3名志愿者中，由于溶血（n=1）和转氨酶无症状性升高（n=2; 1名为戊型肝炎阳性）而停止剂量递增方案。除此之外，递增方案耐受性良好，无药物相关严重不良事件。第1部分中，血红蛋白浓度下降的中位数为3.7 g/dL（范围：2.1 - 5.9;相对下降26% [范围：15 - 40%]）。伯氨喹剂量高达0.87 mg/kg/天，随后可耐受，血红蛋白未出现具有临床意义的进一步福尔斯下降。第2部分中，血红蛋白浓度下降中位数为1.7 g/dL（范围：0.9 - 4.1;相对下降12% [范围：下降7 - 30%]）。递增剂量伯氨喹方案给了7倍以上的药物，但只导致了两倍的血红蛋白decline.Conclusions和InterpretationIn东南亚G6 PDd变异体的患者完全根治治疗可以在三个星期内给予相比，目前的8周方案。
BackgroundPrimaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses ofPlasmodium vivaxmalaria. The 8-aminoquinolines cause dose dependent haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals. G6PDd is common in malaria endemic areas but testing is often not available. As a consequence primaquine is underused.MethodsWe conducted a pharmacometric study to characterise the relationship between primaquine dose and haemolysis in G6PDd. The aim was to explore shorter and safer primaquine radical cure regimens compared to the currently recommended 8-weekly regimen (0.75 mg/kg once weekly), potentially obviating the need for G6PD testing. Hemizygous G6PDd healthy adult Thai and Burmese male volunteers were admitted to the Hospital for Tropical Diseases in Bangkok. In Part 1, volunteers were given ascending dose primaquine regimens whereby daily doses were increased from 7.5 mg up to 45 mg over 15 to 20 days. In Part 2, a single primaquine 45 mg dose was given.Results24 volunteers were enrolled in Part 1, and 16 in Part 2 (13 participated in both studies). In three volunteers, the ascending dose regimen was stopped because of haemolysis (n=1) and asymptomatic increases in transaminases (n=2; one was hepatitis E positive). Otherwise the ascending regimens were well tolerated with no drug-related serious adverse events. In Part 1, the median haemoglobin concentration decline was 3.7 g/dL (range: 2.1 to 5.9; relative decline of 26% [range: 15 to 40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin concentration decline was 1.7 g/dL (range 0.9 to 4.1; relative fall of 12% [range: 7 to 30% decrease]). The ascending dose primaquine regimens gave 7 times more drug but resulted in only double the haemoglobin decline.Conclusions and InterpretationIn patients with Southeast Asian G6PDd variants full radical cure treatment can be given in under three weeks compared with the current 8 week regimen.
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地中海型葡萄糖-6-磷酸脱氢酶缺乏症对间日疟原虫疟疾的保护作用。
影响因子：
7.7
作者：
Awab GR;Aaram F;Jamornthanyawat N;Suwannasin K;Pagornrat W;Watson JA;Woodrow CJ;Dondorp AM;Day NP;Imwong M;White NJ
通讯作者：
White NJ
影响因子：
11.1
作者：
A. Alving;Charles F. Johnson;A. Tarlov;G. Brewer;Kellermeyer Rw;P. Carson
通讯作者：
A. Alving;Charles F. Johnson;A. Tarlov;G. Brewer;Kellermeyer Rw;P. Carson
影响因子：
8
作者：
Karnauskas, R;Niu, Q;Rudin, CM
通讯作者：
Rudin, CM
DOI：
10.1001/jama.1962.03050180034008a
发表时间：
1962-01-01
影响因子：
120.7
作者：
KELLERMEYER, RW;BREWER, GJ;ALVING, AS
通讯作者：
ALVING, AS
影响因子：
15.9
作者：
PIOMELLI, S;CORASH, LM;AMOROSI, EL
通讯作者：
AMOROSI, EL