LACK OF PRESYSTEMIC METABOLISM OF NIFEDIPINE IN THE RABBIT

In humans, oral bioavailability of nifedipine has been reported to be around 60%, although the organ(s) contributing to its first-pass metab olism have not been determined. The aim of this study was to determine in vivo, in anesthetized and conscious rabbits the role of the intest ine, liver, and lungs in the first-pass metabolism of nifedipine. To a ssess the extraction of nifedipine by the intestine, liver, and lungs, nifedipine was administered before and after each organ, and serial b lood samples were withdrawn from an artery. In conscious rabbits, the systemic clearance of nifedipine injected into a lateral vein of an ea r was 14.6 +/- 1.6 ml/min per kg, a value that was slightly decreased by anesthesia. In anesthetized rabbits, compared to the clearance esti mated when nifedipine was administered into the thoracic aorta, the ad ministration of nifedipine into a jugular vein, into the portal vein, or into the duodenum did not increase the value of the systemic cleara nce. In conscious rabbits, the clearance of nifedipine estimated when the drug was administered into the duodenum, the peritoneum, the porta l vein, or into the jugular vein was identical to was metabolized in l iver and intestinal epithelial cells homogenates but not in lungs or k idneys. We concluded that in the rabbit, oral nifedipine is not subjec ted to a first-pass metabolism, even though the intestine and the live r contribute to nifedipine systemic clearance.