Metabolism and biliary excretion of the lipophilic drug molecules, imipramine and desmethylimipramine in the rat—II

Bickel, Marcel H.; Minder, Rudolf E.

doi:10.1016/0006-2952(70)90268-6

Cited by 24 publications

(9 citation statements)

References 13 publications

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“…High levels of dmi in the bile of rats treated with ip have previously been demonstrated by Bickel and Minder. 2 As the volume of distribution of ip and dmi is within the same high range,l, 9 the relatively high peripheral level of dmi presumes a high degree of demethylation which probably occurs in the liver. Thus, there is no evidence that ip is demethylated in the intestinal wall but instead there is evidence of an enterohepatic circulation for both ip and dmi.…”

Section: Discussionmentioning

confidence: 98%

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine

Dencker

Green

et al. 1976

Clin Pharma and Therapeutics

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The intestinal absorption and metabolism of single oral doses of imipramine (ip) The tricyclic antidepressant ip is demethylated in man to the pharmacologically active metabolite dmi.7 Animal studies have indicated the possibility that the demethylation might be dependent on the route of administration. 3 Recent studies of the plasma level have shown that significantly more dmi is formed after oral than after parenteral administration of ip in man.9 Since the absorption of oral ip was found to be almost complete 5 in man, our findings indicate demethylation of the drug before it reaches the systematic circulation, either during passage across the intestinal wall or in the liver.The purpose of our study was to investigate whether demethylation of ip occurs during passage across the intestinal wall. Three human subjects were given single oral doses of ip-hydrochloride (ip-HCI). Portal blood samReceived for publication Oc!. 27, 1975. Accepted for publication Nov. 12, 1975. Reprint requests to: Dr. S. J. Dencker, Lillhagen Mental Hospital, Department n, S-422 03 Hisings Backa 3, Sweden. 584pIes were drawn by transumbilical catheterization. The plasma levels of ip and dmi were simultaneously determined in the portal and in the cubital veins. Material and methodsThe subjects were 3 patients, 2 men and woman, 46 to 54 yr of age. All had been operated upon I yr earlier for carcinoma of the sigmoid. In order to exclude liver metastases, the patients were examined by portography and scintigraphy, with negative results. Liver function studies, including serum bilirubin, alkaline phosphates, lactic dehydrogenase (LDH) , and serum aspartate aminotransferase (ASAT), were within normal limits. At the time of the study the patients were in good general condition and had not received any regular treatment with drugs during the previous 6 moo Single doses of ip-HCI (0.5 mg/kg body weight dissolved in lOO ml of water) were given in the morning, the subjects having fasted overnight.

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Section: Discussionmentioning

confidence: 98%

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine

Dencker

Green

et al. 1976

Clin Pharma and Therapeutics

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“…AND OTHER BILIARY CONSTITUENTS As a result of early studies on the physical state of bile, BR was initially thought to exist in bile in macromolecular complexes with both lipids and proteins (see reference 7 for review). More recently it has been proposed that certain drugs and organic anions in bile (in- cluding BR) are incorporated into the mixed lipid micelles (6)(7)(8)(9). A physical association with the lipid micelles could theoretically diminish the effective activity of these organic anions and xenobiotics in bile, establishing a concentration gradient between the hepatocytes and canalicular fluid that would favor passive diffusion of organic anion monomers from the liver into bile.…”

Section: Interactions Between Organic Anionsmentioning

confidence: 99%

Physical State of Bilirubin and Organic Anions in Bile

Reuben

1984

Hepatology

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“…The procedures and apparatus described by Miller, Bly, Watson & Bale (1951) and Bickel & Minder (1970) were adopted with certain modifications. The perfusate consisted of equal volumes of heparinized whole rat blood and Krebs-Henseleit buffer and was circulated by means of a roller pump (MHRE 88,England (1966) except that the samples were mixed with Instagel (Packard) after oxidation.…”

Section: Isolated Perfused Rat Livermentioning

confidence: 99%

EFFECT OF ETHER ANAESTHESIA ON PHARMACOKINETICS OF N‐(2 HYDROXY ETHYL) 2‐PHENYL ETHYL CARBAMATE: INHIBITION OF ITS ENTEROHEPATIC CIRCULATION

Obianwu

1974

British J Pharmacology

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1The effect of the ether anaesthesia on the plasma half-life of N-(2 hydroxy ethyl) 2-phenyl ethyl carbamate has been studied in rats. 2 The plasma half-life of the carbamate was considerably shorter in animals anaesthetized with ether prior to drug administration than in control rats. 3 The longer plasma half-life of the carbamate in control animals was shown to be due to enterohepatic circulation. 4 Inhibition of this phenomenon by ether was responsible for the shorter plasma half-life of the carbamate in animals anaesthetized with this agent before drug administration. 5 The possible mechanisms by which the ether-induced effect is brought about are discussed.

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Metabolism and biliary excretion of the lipophilic drug molecules, imipramine and desmethylimipramine in the rat—II

Cited by 24 publications

References 13 publications

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine

Intestinal absorption, demethylation, and enterohepatic circulation of imipramine

Physical State of Bilirubin and Organic Anions in Bile

EFFECT OF ETHER ANAESTHESIA ON PHARMACOKINETICS OF N‐(2 HYDROXY ETHYL) 2‐PHENYL ETHYL CARBAMATE: INHIBITION OF ITS ENTEROHEPATIC CIRCULATION

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