Effects of diethyl ether anaesthesia on the pharmacokinetics of antipyrine and paracetamol in the rat

Johannessen, W; Gadeholt, G; Aarbakke, Jarle

doi:10.1111/j.2042-7158.1981.tb13805.x

Cited by 27 publications

(5 citation statements)

References 8 publications

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“…Enzyme induction is not likely to occur, since more time than the period between anaesthesia and liver homogenisation is needed for the elevation of enzyme levels. Ether, however, may inhibit biotransformation reactions in vivo, but only after prolonged anaesthesia (Johannessen et al 1981). It is not very likely that this has occurred in our experiments, since the bulk of the ether used will be evaporated during microsome preparation.…”

Section: Discussionmentioning

confidence: 66%

Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver

et al. 1993

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The hamster is known to display very high rates of monooxygenase-mediated biotransformation. In comparison with other species little knowledge has been gathered with respect to the nature of its cytochrome P450 enzymes and their respective inducibility. We studied the consequences of induction of P450 enzymes in rats and Syrian golden hamsters using the regioselective oxidative O-demethylation of the coumarin derivative scoparone. This metabolic conversion indicates differential effects of P450 inducers in the rat, in which various types of inducers cause different shifts in the isoscopoletin/scopoletin metabolite ratio (I/S-ratio). Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats. In rat liver microsomes total demethylation rates of scoparone increased upon in vivo treatment with phenobarbital or beta-naphthoflavone. Phenobarbital reduced the I/S-ratio whereas beta-naphthoflavone caused an increase in this ratio. In hamster liver microsomes both phenobarbital and beta-naphthoflavone treatments resulted in a decrease in the I/S ratio. In this species the total scoparone demethylation rate was not much affected by phenobarbital, but beta-naphthoflavone caused a huge increase in over-all scoparone biotransformation. In both species, dexamethasone, isoniazid and clofibrate were much less effective. In contrast to the rat, in the hamster the scoparone biotransformation profile cannot be used to differentiate between phenobarbital- or beta-naphthoflavone-treated animals.

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Section: Discussionmentioning

confidence: 66%

Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver

et al. 1993

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“…For ethical considerations, diethyl ether was administrated during the periods of blood sampling. According to previous publications [36,37], it is no obvious influence of diethyl ether on the rates of distribution and redistribution of drugs. However, this anesthesia can obviously inhibit the clearance of the drugs because it can interfere the metabolism and oxidation of the drugs in the liver.…”

Section: Discussionmentioning

confidence: 96%

“…However, this anesthesia can obviously inhibit the clearance of the drugs because it can interfere the metabolism and oxidation of the drugs in the liver. Therefore, diethyl ether, when used as an anesthetic in the pharmacokinetic research of drugs, is suggested for use with drugs with longer half-lives rather than those with short elimination half-lives [36]. Although azalomycin F presents short elimination half-lives (Table 2), the inhibition by diethyl ether of the clearance of drugs may be not suitable for studying azalomycin F, as it is stabile in the liver homogenate.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats

Zhao

et al. 2021

Molecules

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As antimicrobial resistance has been increasing, new antimicrobial agents are desperately needed. Azalomycin F, a natural polyhydroxy macrolide, presents remarkable antimicrobial activities. To investigate its pharmacokinetic characteristics in rats, the concentrations of azalomycin F contained in biological samples, in vitro, were determined using a validated high-performance liquid chromatography–ultraviolet (HPLC-UV) method, and, in vivo, samples were assayed by an ultra-high performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method. Based on these methods, the pharmacokinetics of azalomycin F were first investigated. Its plasma concentration-time courses and pharmacokinetic parameters in rats were obtained by a non-compartment model for oral (26.4 mg/kg) and intravenous (2.2 mg/kg) administrations. The results indicate that the oral absolute bioavailability of azalomycin F is very low (2.39 ± 1.28%). From combinational analyses of these pharmacokinetic parameters, and of the results of the in-vitro absorption and metabolism experiments, we conclude that azalomycin F is absorbed relatively slowly and with difficulty by the intestinal tract, and subsequently can be rapidly distributed into the tissues and/or intracellular f of rats. Azalomycin F is stable in plasma, whole blood, and the liver, and presents plasma protein binding ratios of more than 90%. Moreover, one of the major elimination routes of azalomycin F is its excretion through bile and feces. Together, the above indicate that azalomycin F is suitable for administration by intravenous injection when used for systemic diseases, while, by oral administration, it can be used in the treatment of diseases of the gastrointestinal tract.

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“…1983). Diethyl ether has been shown to cause similar effects both in vivo (Johannessen et al 1981) and in isolated hepatocytes (Aune et al 1981a). Also the rate of ethanol oxidation decreased in isolated hepatocytes in the presence of ether (Aune et al 1981b).…”

mentioning

confidence: 90%

Acute Interaction of Halothane and Enflurane with the Metabolism of Ethanol in Isolated Hepatocytes and Liver Cytosol Preparations from the Rat

Aune¹,

Normann²,

Olsen³

et al. 1985

Acta Pharmacologica et Toxicologica

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The effects of halothane and enflurane on ethanol (40 mM) oxidation were studied in isolated rat hepatocytes. Anaesthetic (halothane, enflurane and diethyl ether) effect on the activity of alcohol dehydrogenase (ADH) was studied in incubations of cytosol preparations from rat liver. Mean rates of ethanol metabolism ranged from 0.44 to 0.49 μmol ethanol metabolized/mg cell protein/hour in control hepatocytes from fasted and fed animals. These rates were enhanced by 2‐ and 3‐fold in hepatocytes from fed and fasted animals, respectively, when pyruvate (5 mM) was added. Halothane and enflurane both caused dose dependent inhibition of ethanol metabolism (15‐40%) in all hepatocytes without exogenous addition of pyruvate. The inhibitory effect was present also after pyruvate stimulation in hepatocytes from fasted animals, but disappeared in hepatocytes from fed animals when pyruvate was added. The rate of ethanol oxidation by cells from fed rats was enhanced by approximately 40% when the concentration of ethanol was increased from 20 mM to 80 mM. The anaesthetic inhibition of ethanol metabolism was about 20% more pronounced at the higher ethanol concentration compared to the lower concentration when no pyruvate was added. In the presence of pyruvate the effect of anaesthetics was again reversed regardless of ethanol concentration. Halothane (2 mM) and enflurane (2 mM) both caused about 25% inhibition of the ADH‐activity in cytosol preparations while ether (30 mM) caused more than 50% inhibition. No inhibition of hepatocyte uptake of ethanol was caused by any of the three anaesthetics. It was concluded that the volatile anaesthetic agents in addition to their well known membrane effects also seem to be able to interfere directly with the activity of the non‐membrane related enzyme ADH.

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Effects of diethyl ether anaesthesia on the pharmacokinetics of antipyrine and paracetamol in the rat

Cited by 27 publications

References 8 publications

Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver

Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver

Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats

Acute Interaction of Halothane and Enflurane with the Metabolism of Ethanol in Isolated Hepatocytes and Liver Cytosol Preparations from the Rat

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