Vásquez Laura, Scorza Dagert José V, Scorza José V, Vicuña-Fernández Nelson, de Peña Yaneira Petit, López Sabrina, Bendezú Herminia, Rojas Elina, Vásquez Libia, Pérez Belén
University of The Andes, Faculty of Medicine, Valera School of Medicine, Laboratory of Pharmacology, Valera, Venezuela ; University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
Curr Ther Res Clin Exp. 2006 May;67(3):193-203. doi: 10.1016/j.curtheres.2006.06.005.
Pentavalent antimony (SbV) has demonstrated therapeuticeffectiveness against clinical manifestations of leishmaniasis, an infection caused by Leishmania, a genus of flagellate protozoa comprising parasites of worldwide distribution. Approximately 1.8 million new cases are reported annually.
The aim of this study was to assess the pharmacokinetics of the investigational generic SbV, Ulamina (pentachloride of antimony + N-methylglucamine), in healthy adult volunteers.
In this study, SbV was administered IM as a single 5-mg/kg dose.Blood samples were collected at 0.25, 0.75, 1, 2, 4, 8, 12, and 24 hours after administration; urine samples were collected at 6-hour intervals during the 24-hour postadministration period. Determination of trivalent antimony, SbV, and total antimony concentrations in blood and urine samples was carried out using atomic absorption spectrometry. Clinical history was reviewed and the subjects were monitored before and after administration of SbV using physical examination, weight, and hepatic- and renal-function studies. The pharmacokinetic parameters calculated were Cmax, Tmax, absorption constant (Ka), elimination constant (Kel), AUC2-24h, AUC0-∞, elimination phase (t½β), volume of distribution (Vd), and urinary excretion rate.
Five subjects (3 men, 2 women; mean age, 28 years [range, 18-34 years]) were included in the study. One hour after drug administration the following values were obtained: Cmax, 1.1 μg/mL; Tmax, 1.3 hours; Ka, 1.87 hours; Kel, 0.043 hours; AUC0-24h, 12.26 μg/mL · h; AUC0-∞, 19.84 μg/mL · h; t½β, 17.45 hours; Vd, 6.6 L/kg; and urinary excretion rate, 2.8 μg/h; these were mean values for the entire study group. The single dose was well tolerated by all subjects.
The investigational generic SbV, Ulamina, was associated with linearelimination after IM administration of a single 5-mg/kg dose. A 2-compartment pharmacokinetic model was observed in these volunteers; the mean t½β, was 17.45 hours and the mean Vd was 6.6 L/kg.
五价锑（SbV）已被证明对利什曼病的临床表现具有治疗效果，利什曼病是由利什曼原虫属引起的一种感染，利什曼原虫属是一种鞭毛虫原生动物，其寄生虫分布于世界各地。每年报告的新病例约为180万例。
本研究的目的是评估研究用通用型SbV（乌拉米纳，五氯化锑+N-甲基葡糖胺）在健康成年志愿者中的药代动力学。
在本研究中，以5mg/kg的单次剂量肌肉注射SbV。给药后0.25、0.75、1、2、4、8、12和24小时采集血样；给药后24小时内每隔6小时采集尿样。使用原子吸收光谱法测定血样和尿样中的三价锑、SbV和总锑浓度。回顾临床病史，并在SbV给药前后通过体格检查、体重以及肝肾功能研究对受试者进行监测。计算的药代动力学参数为Cmax、Tmax、吸收常数（Ka）、消除常数（Kel）、AUC2-24h、AUC0-∞、消除相（t½β）、分布容积（Vd）和尿排泄率。
5名受试者（3名男性，2名女性；平均年龄28岁[范围18 - 34岁]）纳入本研究。给药1小时后获得以下值：Cmax为1.1μg/mL；Tmax为1.3小时；Ka为1.87小时；Kel为0.043小时；AUC0-24h为12.26μg/mL·h；AUC0-∞为19.84μg/mL·h；t½β为17.45小时；Vd为6.6L/kg；尿排泄率为2.8μg/h；这些是整个研究组的平均值。所有受试者对单次剂量耐受性良好。
研究用通用型SbV乌拉米纳在肌肉注射5mg/kg单次剂量后呈现线性消除。在这些志愿者中观察到二室药代动力学模型；平均t½β为17.45小时，平均Vd为6.6L/kg。
