Pharmacology of quinacrine hydrochloride with emphasis on its use as a tubal occluding agent.

The pharmacokinetic properties of quinacrine hydrochloride following intrauterine injection were investigated in cynomolgus monkeys. The 1st study compared intravascular and intrauterine quinacrine administration. Following injection of 30 mg quinacrine solution concentrations were 149 +or- 42 ng/ml in the intravascular group and 77.1 +or- 37.0 ng/ml in the intrauterine group at 0.5 hours. The rate of decline was similar in both groups. 24 hours after injection quinacrine was found in the reproductive organs (including the isthmus and ampulla of the oviduct) as well as many other organs such as lung adrenal kidney and pancreas. In the 2nd study intrauterine injections of quinacrine were administered to pregnant monkeys. A 30 mg dose resulted in plasma concentrations comparable to those in nonpregnant monkeys receiving intravascular administration of the same dose. Of concern was the death of 1 pregnant monkey 48 hours after injection. This animal had a 445 ng/ml plasma quinacrine concentration 0.5 hours after injection which was higher than any other concentration and urine could not be obtained. Impaired clearance of the drug may account for the high plasma levels in this case. The 3rd study aimed to determine toxicity in the case of spill of quinacrine through the oviducts into the peritoneal cavity or perforation of the uterus with direct application of the drug into this cavity. Application of 30 mg quinacrine into the peritoneal cavity revealed no adverse effects. However when 3 monkeys received 250 mg of the drug 2 died with 2 hours and the 3rd had a seizure. 3 additional monkeys who were given a 125 mg dose survived but 1 demonstrated slight limb tremors. All showed behavior suggestive of abdominal pain. These studies indicate 3 effects that raise concerns about the use of quinacrine as a tubal occlusion agent: abdominal pain central nervous system stimulation and death following drug injection. The abdominal pain is thought to be due to an inflammatory response of the peritoneum to the drug. Central nervous system excitation has been reported previously in people receiving quinacrine for treatment of malaria and in women receiving the drug as a tubal occlusion agent. No drug-related deaths have been reported in humans. It is noted that the pellet that caused death in the monkey was on a body weight basis 17 times the dose normally given to women and the drug was placed directly into the peritoneal cavity.