长效醋酸甲孕酮用于男性避孕的药代动力学及抑制精子发生的剂量研究  

A Pharmacokinetic Study of DMPA and Dose-Finding Study to Suppress Spermatogenesis in Normal Chinese Men

作　　者：谷翊群[1] 袁冬[1] 童建孙 马鼎志 王兴海 

机构地区：[1]国家人口计生委科学技术研究所,北京100081 [2]江苏省人口与计划生育科研所

出　　处：《中国计划生育学杂志》2005年第10期590-593,共4页Chinese Journal of Family Planning

基　　金：美国CONRAD基金会资助;项目号:CIG-00-52

摘　　要：比较两种剂量长效醋酸甲孕酮(DMPA)用于男性避孕的药代动力学特性以及抑制精子发生的效果,推荐进一步临床试验配伍剂量和注射间隔。方法:将筛选合格的正常志愿者30名随机分成3组(每组10名),A组150mgDMPA+1000mg十一酸睾酮酯(TU);B组300mgDMPA+1000mgTU;C组单独注射1000mgTU(为对照组)。A和B组受试者按要求接受指定的配伍剂量注射。注射前后每周静脉取血,直至8周,进行血MPA测定。然后,受试者继续每8周接受指定的配伍剂量或TU单独注射,直至完成24周的治疗期,并按要求定期随访进行精液分析及其它安全性指标监测,最后完成24周的恢复期随访。结果:受试者的各项参数在各组内均匀分布。尽管B组较A组有相对较高的血药浓度,但药代动力学的各项参数在两组之间无显著性差异。A、B和C组抑制精子发生起效时间分别为80±5d、83±8d和92±6d,各组间没有统计学差异。尽管合用组比单用组有更持久地抑制精子发生的趋势,但各组之间没有统计学差异。合用组能更加有效地抑制促性腺激素的分泌,与单用组之间有显著性差异;促性腺激素的抑制程度与配伍中DMPA的剂量无关。结论:A与B组在药代动力学的各项参数与抑制精子发生的疗效上无显著性差异。150mgDMPA与1000mgTU或更长效的雄激素联合应用可能成为2～3个月肌肉注射一针的男性避孕药的最佳剂量组合。推荐使用低剂量DMPA配伍TU进行临床避孕有效性的研究。Objective： To compare pharmacokinetics and efficacy of spermatogenesis suppression by two doses of depot medroxyprogesterone acetate （DMPA） combined with testosterone undecanoate （TU） in normal Chinese men and to recommend dose - combination and injection intervals for further clinical trial. Methods ： After screening, thirty healthy volunteers were enrolled and were randomly assigned to one of 3 dose - groups, （n = 10/group） ： 150 mg DMPA plus 1000 mg TU （Group A） ; 300 mg DMPA plus 1000 mg TU; （Group B） ; 1000 mg TU alone as a control （Group C）. Group A and B were given assigned dose- combination by intramuscular injection. Their blood samples were collected for serum MPA assays at weekly intervals for 8 successive weeks from the beginning of the treatment period. Thereafter, all volunteers continued to receive assigned dose - combination or TU alone injections at 8 - week intervals until completion of 24 - week treatment period. During the treatment period, all volunteers attended the clinic every 4 weeks to undergo physical and andrological examinations. A semen sample and a fasting blood sample were collected for safety monitoring until the end of recovery period. Results： All parameters of volunteers were fairly well - distributed among the 3 groups. There were no significant differences in all pharmacokinetic parameters between the two groups although Group B had relatively higher serum MPA concentrations than Group A. The mean waiting time for the onset of spermatogenic suppression was 80±5, 83±8 and 92 ± 6 days for Groups A, B and C, respectively; these values were not statistically different. Significant differences in the ability of the regimens to suppress gonadotropins were found between the DMPA plus TU combination groups and the TU alone group; there was no dose - response relationship between the degree of suppression of serum LH and FSH and the amount of DMPA administered. Conclusion： 150mg DMPA, in combination with TU or a more long- acting androgen, could pr

关 键 词：孕激素 雄激素 促性腺激素 精子密度 无精子 严重少精子 药代动力学 男性避孕药 醋酸甲孕酮 精子发生 

分 类 号：R96[医药卫生—药理学]