甲氟喹在巴西男性受试者中的I期临床试验。

A phase I clinical trial of mefloquine in Brazilian male subjects.

作者信息

de Souza J M

出版信息

Bull World Health Organ. 1983;61(5):809-14.

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2536169/

Abstract

A double-blind, randomized phase I clinical trial was carried out to compare mefloquine with sulfadoxine-pyrimethamine for safety and tolerance. Twenty adult male Brazilian subjects from areas endemic for malaria were studied for a period of 66 days, which included 2 days of basal studies and a 63-day follow-up after drug administration. Subjects received either mefloquine, given as a single oral dose of 1000 mg (4 x 250-mg tablets) or sulfadoxine-pyrimethamine (2 tablets, each containing 500 mg of sulfadoxine plus 25 mg of pyrimethamine). Clinical examination, electrocardiogram, chest X-ray, and haematological, biochemical, stool, and urine analyses were carried out before drug administration and at various intervals afterwards. Peripheral blood smears were examined for malarial parasites.Both drugs were well tolerated and safe as seen from the absence of drug-induced changes in the various laboratory assay results. There was an improvement in body weight, red blood cell count, haemoglobin, and erythrocyte volume fraction values for all patients during the study. In subjects who had positive smears for Plasmodium falciparum, mefloquine produced complete clearance on day 1 with an S-type response (3 cases). Sulfadoxine-pyrimethamine produced complete clearance on day 2 in 5 subjects, but a delayed RI-type response (recrudescence) was observed in 2 cases and an early RI response in one case. P. vivax relapses occurred in both groups. Side-effects of mefloquine included mild diarrhoea (20%) and dizziness (40%); dizziness was also observed with sulfadoxine-pyrimethamine (20%). In both groups, side-effects were mild, short-lived and needed no specific treatment.Thus, mefloquine in an oral dose of 1000 mg was found to be well tolerated and safe in adult male Brazilian volunteers from endemic areas. No drug-related adverse reactions were observed. In cases where P. falciparum infection was present, there was a complete parasite clearance with no recrudescence.

摘要

开展了一项双盲、随机I期临床试验，以比较甲氟喹和磺胺多辛-乙胺嘧啶的安全性和耐受性。对来自疟疾流行地区的20名成年巴西男性受试者进行了为期66天的研究，其中包括2天的基础研究以及给药后63天的随访。受试者分别接受甲氟喹（单次口服剂量为1000 mg，即4片250 mg片剂）或磺胺多辛-乙胺嘧啶（2片，每片含500 mg磺胺多辛加25 mg乙胺嘧啶）。在给药前及给药后的不同时间间隔进行临床检查、心电图、胸部X线检查以及血液学、生化、粪便和尿液分析。检查外周血涂片以查找疟原虫。从各项实验室检测结果未出现药物诱导的变化来看，两种药物耐受性良好且安全。在研究期间，所有患者的体重、红细胞计数、血红蛋白和红细胞体积分数值均有所改善。在恶性疟原虫涂片呈阳性的受试者中，甲氟喹在第1天实现了完全清除，呈现S型反应（3例）。磺胺多辛-乙胺嘧啶在第2天使5名受试者实现了完全清除，但在2例中观察到延迟的RI型反应（复发），1例出现早期RI反应。两组均出现间日疟复发。甲氟喹的副作用包括轻度腹泻（20%）和头晕（40%）；磺胺多辛-乙胺嘧啶也观察到头晕（20%）。在两组中，副作用均较轻，持续时间短，无需特殊治疗。因此，发现口服剂量为1000 mg的甲氟喹在来自流行地区的成年巴西男性志愿者中耐受性良好且安全。未观察到与药物相关的不良反应。在存在恶性疟原虫感染的病例中，实现了寄生虫的完全清除且无复发。