Lack of presystemic metabolism of nifedipine in the rabbit

Abstract

In humans, oral bioavailability of nifedipine has been reported to be around 60%, although the organ(s) contributing to its first-pass metabolism have not been determined. The aim of this study was to determine in vivo, in anesthetized and conscious rabbits the role of the intestine, liver, and lungs in the first-pass metabolism of nifedipine. To assess the extraction of nifedipine by the intestine, liver, and lungs, nifedipine was administered before and after each organ, and serial blood samples were withdrawn from an artery. In conscious rabbits, the systemic clearance of nifedipine injected into a lateral vein of an ear was 14.6 +/- 1.6 ml/min per kg, a value that was slightly decreased by anesthesia. In anesthetized rabbits, compared to the clearance estimated when nifedipine was administered into the thoracic aorta, the administration of nifedipine into a jugular vein, into the portal vein, or into the portal vein, or into the duodenum did not increase the value of the systemic clearance. In conscious rabbits, the clearance of nifedipine estimated when the drug was administered into the duodenum, the peritoneum, the portal vein, or into the jugular vein was identical to the clearance calculated when the drug was injected into the thoracic aorta. In vitro, nifedipine was metabolized in liver and intestinal epithelial cells homogenates but not in lungs or kidneys. We concluded that in the rabbit, oral nifedipine is not subjected to a first-pass metabolism, even though the intestine and the liver may contribute to nifedipine systemic clearance.

Grapefruit juice and orange juice effects on the bioavailability of nifedipine in the rat

“…Interestingly, du Souich et al [64] noted a lack of intestinal, hepatic, or pulmonary presystemic metabolism of nifedipine in the rabbit, leading to speculation by the authors that nifedipine may be decomposed in the GI lumen of rats and humans to account for its poor oral bioavailability. The results of the present study seem to contradict this theory, as nifedipine appears to be completely absorbed from the GI tract of rats when coadministered with GJC.…”

Extrahepatic First-Pass Metabolism of Nifedipine in the Rat

“…8 In addition, to our knowledge, nifedipine has not been shown to decompose in the lumen of the GI tract of any animal species although this mechanism has been proposed to explain the poor bioavailability of nifedipine in rats and human beings. 33 Hence, assuming F L and F G are unity, the predicted F of the drug was calculated from…”

Isolation and characterization of metabolites of centpropazine in rat liver, intestine, and red blood cell homogenates

“…It was then homogenized in 0.05 M phosphate buffer containing 1.15% potassium chloride (pH 7.4) using a Potter-Elvehjem apparatus (25% w/v tissue). 5 The homogenate was centrifuged at 9000g (48C) and the supernatant was stored at 48C until use. The viability of the preparation was confirmed by estimating the cytochrome P450 content 6 in microsomes prepared from S9 fraction.…”