Dubin N H, Parmley T H, Ghodgaonkar R B, Strandberg J D, Rosenshein N B, King T M
Contraception. 1984 Jun;29(6):561-71. doi: 10.1016/s0010-7824(84)80018-9.
Cynomolgus monkeys were used to screen for chemicals which potentially could be used as tubal occluding agents. Intrauterine administrations of solution or pellets of tetracycline and its analogues (100 mg doses) were tested for their effects on morphologic changes in the reproductive tract of monkeys. These effects were compared to monkeys receiving intrauterine administration of quinacrine pellets (36 mg) since quinacrine has been used successfully in the clinical setting. Blood levels of drugs, blood chemistry and hematology determinations and liver and kidney pathology data were also obtained as indices for toxicity. Morphologic damage to the uterine lining and intramural section of the tube (including necrosis, inflammation or scarring) was elicited by intrauterine tetracycline and doxycycline in the same frequency and severity as quinacrine. In contrast, saline or sham control monkeys showed no morphological damage of the tube or uterus. Although all drugs could be detected in the blood 4 hours after intrauterine administration, levels were near or below the limit of detection by one week. No evidence was found for toxicity of tetracycline or its analogues for the dosage given. Because of these results and the extensive literature on tetracycline toxicity, further studies should be directed toward the use of tetracycline as a sterilizing agent in women.
食蟹猴被用于筛选可能用作输卵管阻塞剂的化学物质。对四环素及其类似物的溶液或丸剂进行宫内给药（100毫克剂量），测试其对猴生殖道形态变化的影响。将这些影响与接受宫内给予喹吖因丸剂（36毫克）的猴子进行比较，因为喹吖因已在临床环境中成功使用。还获得了药物的血液水平、血液化学和血液学测定以及肝脏和肾脏病理学数据作为毒性指标。宫内给予四环素和强力霉素引起的子宫内膜和输卵管壁内段的形态学损伤（包括坏死、炎症或瘢痕形成）与喹吖因的频率和严重程度相同。相比之下，生理盐水或假手术对照猴未显示输卵管或子宫的形态学损伤。虽然宫内给药4小时后所有药物均可在血液中检测到，但到一周时水平接近或低于检测限。未发现所给剂量的四环素或其类似物有毒性证据。鉴于这些结果以及关于四环素毒性的大量文献，进一步的研究应朝着将四环素用作女性绝育剂的方向进行。
