15 Quinacrine Hydrochloride : Future Research

Without doubt, there is a need and a demand for a chemical method of tubal sterilization. Chemicals of various categories, including caustic, sclerosing, granuloma-producing, and cytotoxic agents and tissue adhesives have been tested in both animal models and humans.2 The most effective agent appears to be quinacrine, and, depending on the mode of delivery, it can cause bilateral tubal closure rates in excess of 90%. Clinically, quinacrine has been used in several developing countries. Efforts have been directed toward improving the efficacy of quinacrine by manipulating the mode of delivery. One approach has been a change from its administration as a slurry to a compacted pellet. Vor T-shaped IUD vectors, with quinacrine located at the tips, have been especially designed to ensure delivery of the drug to the cornual region of the uterus near the uterotubal junction. As efficacy of quinacrine sterilization improves, safety comes to the fore. In evaluating the elusive risk/benefit ratio of a drug treatment, the therapeutic index is an important consideration. The therapeutic index is the relationship between the dose of a drug that produces an undesirable effect, compared with the dose that produces the desired effect. That index represents, in essence, the “margin of safety” of the drug. A low index, that is, one in which the toxic dose is very close to the effective dose, may be acceptable in the treatment of a life-threatening disease. Thus, digitalis, which has a very low therapeutic index, is nevertheless an acceptable agent for the treatment of congestive heart failure. In regard to quinacrine, there are numerous known toxic effects; yet, these were of minor importance when this agent was used to treat patients with malaria. However, the risk/benefit assessment of a drug for the treatment or prevention of a debilitating disease like malaria may not be the same as when the agent is used for voluntary tubal sterilization. As an agent for chemical sterilization, it must be assessed against the risks of current methods of surgical contraception, as well as against the risks of other methods of contraception, and of pregnancy itself.