Abstract

PIP: Contraceptive natural steroids, such as progesterone and estradiol, are ineffective when administered orally because of extensive metabolism in the gastrointestinal (GI) tract during absorption and first-pass metabolism. Consequently, highly potent and potentially harmful synthetic steroids are now being used in oral dosage forms. The nasal route was examined for the purpose of enhancing progesterone bioavailability from nonparenteral routes. Earlier studies revealed that propranolol is absorbed efficiently from the nasal mucosa of rats and dogs. Sprague-Dawley male rats, 300 g, were anesthetized with pentobarbital sodium. 4-6 rats were used for each dose and for each administration route. For nasal administration, 3 doses of 50, 100, and 150 mc of progesterone in 0.1 ml of 1% polysorbate 80-saline solution were administered to the nasal cavity of each rat by a micropipet according to the procedure described previously. For intravenous administration, the same doses were injected through the femoral vein. For intraduodenal administration, the abdomen was opened by a midline incision, and the 50 mc dose in 0.1 ml of 1% polysorbate 80-saline solution was injected directly through the duodenum. After administration, 0.2 ml of blood was sampled periodically from the femoral aorta. The blood drug levels after nasal administration increased rapidly and reached the peak level within 6 minutes, whereas the intraduodenal administration resulted in considerably lower blood levels. Study results indicate that the natural contraceptive steriod, progesterone, is absorbed rapidly from the nasal mucosa into systemic blood without first-pass metabolism and that nasal administration is superior to the intraduodenal route.