Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria.
Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria.
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DOI：
10.1186/1475-2875-6-70
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发表时间：
2007-05-25
期刊：
影响因子：
3
通讯作者：
Hutchinson D
中科院分区：
文献类型：
--
作者：
Na-Bangchang K;Ruengweerayut R;Karbwang J;Chauemung A;Hutchinson D
该研究调查了急性无并发症恶性疟疾患者单独使用磷司米霉素和与克林霉素联合使用时的药代动力学。分别从泰国Tak省梅索医院门诊部招募符合入组标准的急性无并发症恶性疟原虫疟疾患者15例和18例。患者接受磷司米多霉素单药治疗，剂量为1，200 mg，每8小时1次，持续7天（n = 15）或磷司米多霉素（900 mg，每12小时1次，持续7天）和克林霉素（600 mg，每12小时1次，持续7天）联合治疗（n = 18）。在给药期间采集血液样本用于克林霉素和/或磷咪霉素的药代动力学研究，并采集24小时尿液样本。疗效评估包括临床和寄生虫学评价。根据临床和实验室研究评估安全性和耐受性。磷咪霉素的单药和联合治疗方案均耐受良好，无严重不良事件。磷司米霉素和克林霉素联合治疗被证明是非常有效的，治愈率为100%，而单药治疗的治愈率为22%（28天随访）。除了Vz/F和CL/F在联合治疗方案中显著较小外，单药和联合治疗后的磷咪霉素药代动力学相似。磷司米霉素和克林霉素的血药浓度-时间曲线与一级吸收和消除以及吸收滞后时间的一室开放模型最佳拟合。在第二次或第三次给药时，磷咪霉素和克林霉素的血浆浓度达到稳态。多次给药期间无剂量蓄积证据。在单药治疗和联合治疗后，尿中磷霉素的回收率分别为18.7%和20%。磷司米霉素-克林霉素联合治疗的药代动力学剂量优化，疗程不超过三天，需要获得一个方案，这是安全的，并产生100%治愈多重耐药恶性疟原虫。
The study investigated the pharmacokinetics of fosmidomycin when given alone and in combination with clindamycin in patients with acute uncomplicated falciparum malaria. A total of 15 and 18 patients with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment criteria were recruited from out-patient department of Mae Sot Hospital, Tak Province, Thailand. Patients were treated with monotherapy with fosmidomycin at the dose of 1,200 mg every 8 hours for 7 days (n = 15) or combination therapy with fosmidomycin (900 mg every 12 hours for 7 days) and clindamycin (600 mg every 12 hours for 7 days) (n = 18). Blood samples were taken for pharmacokinetic investigations of clindamycin and/or fosmidomycin and 24-hour urine samples were collected during dosing period. Efficacy assessments included clinical and parasitological evaluation. Safety and tolerability were assessed based on clinical and laboratory investigations. Both mono- and combination therapy regimens of fosmidomycin were well tolerated with no serious adverse events. Combination therapy with fosmidomycin and clindamycin was proven highly effective with 100% cure rate, whereas cure rate of monotherapy was 22% (28-day follow up). Pharmacokientics of fosmidomycin following mono- and combination therapy were similar except Vz/F and CL/F, which were significantly smaller in the combination regimen. Plasma concentration-time profiles of both fosmidomycin and clindamycin were best fit with a one-compartment open model with first-order absorption and elimination and with absorption lag time. Steady-state plasma concentrations of fosmidomycin and clindamycin were attained at about the second or third dose. There was no evidence of dose accumulation during multiple dosing. Urinary recovery of fosmidomycin was 18.7 and 20% following mono- and combination therapy, respectively. Pharmacokinetic dose optimization of fosmidomycin-clindamycin combination therapy with the course of treatment of not longer than three days is required to obtain a regimen which is safe and produced 100% cure for multidrug-resistant P. falciparum.
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影响因子：
2.9
作者：
DEHAAN, RM;METZLER, CM;VANDENBOSCH, WD
通讯作者：
VANDENBOSCH, WD
影响因子：
4.9
作者：
NEU, HC;KAMIMURA, T
通讯作者：
KAMIMURA, T
影响因子：
3.1
作者：
WAGNER, JG;NOVAK, E;LUMMIS, WL
通讯作者：
LUMMIS, WL
影响因子：
6.4
作者：
Borrmann, S;Adegnika, AA;Kremsner, PG
通讯作者：
Kremsner, PG
影响因子：
2.2
作者：
Cheoymang, Anurak;Hudchinton, David;Na-Bangchang, Kesara
通讯作者：
Na-Bangchang, Kesara