Cimetidine and omeprazole have different effects on hepatic extraction of lidocaine in rats

Bruck, Rafael; Krepel, Z.; Bar‐Meir, Simon

doi:10.1016/0016-5085(90)90981-6

Cited by 11 publications

(7 citation statements)

References 13 publications

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“…Sur vival probability in the first 20 days posttrans plantation was also predicted well using this technique. However, the results from other studies have not been as favorable [53][54][55][67][68][69], When assessing liver function posttrans plantation, MEGX formation as well as ICG clearance have permitted the early differenti ation of patients with a good from those with a poor outcome [70]. Since the GEC (which measures metabolic activity) remains stable postoperatively, the reduction in MEGX for mation and ICG clearance may relate more to a fall in hepatic blood flow rather than to a change in metabolic status of the liver per se.…”

Section: Lidocainementioning

confidence: 37%

“…Stress and infection, not to mention reduced protein synthesis in cir rhosis [52], may thus have confounding ef fects. A similar problem applies to CYP3A4 the activity of which may be affected by drugs such as cimetidine and omeprazole (via inhi bition) or by smoking (via induction) [53,54], However, smoking does not appear to alter MEGX formation significantly [55], The mi crosomal content of CYP3A4 also varies con siderably (by over 9-fold), which further com promises the use of this test [48]. Adverse side effects with lidocaine are fortunately rare [50], Initially, lidocaine clearance itself was used as a quantitative test of liver function [56], but in 1987 Oellerich et al [57] first reported a simplified technique of measuring MEGX levels at 15 and 30 min (as well as at other time intervals) following a 1 mg/kg bo lus intravenous injection of lidocaine.…”

Section: Lidocainementioning

confidence: 99%

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Update on the Use of Metabolic Probes to Quantify Liver Function: Caffeine versus Lidocaine

Ziebell

Shaw-Stiffel²

1995

Dig Dis

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The search continues for a safe, accurate and reliable method to quantify liver function similar in principle to renal creatinine clearance or pulmonary function spirometry tests. When evaluating patients in the more advanced stages of chronic liver disease, one’s clinical judgement regarding the degree of liver dysfunction usually suffices, but in patients with early or only intermediate disease, an estimate based on routine blood tests and/or clinical severity scores is often unreliable. A more quantitative approach under investigation at present has been to monitor specific pharmacokinetic parameters of ‘probe’ drugs metabolized primarily by hepatic cytochrome P-450. These parameters include the plasma or salivary clearance rate of the parent compound and/or the formation rate of its metabolites. Following a review of basic hepatic pharmacology relevant to this topic, we shall explore the advantages and disadvantages of two ‘metabolic probes’ that have shown the most promise to date, caffeine and lidocaine.

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Section: Lidocainementioning

confidence: 37%

Section: Lidocainementioning

confidence: 99%

Update on the Use of Metabolic Probes to Quantify Liver Function: Caffeine versus Lidocaine

Ziebell

Shaw-Stiffel²

1995

Dig Dis

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“…In our study, there is no positive control. However, we used rat interferon of the same manufacturer as was used by Craig et al (9), and, in a previous paper by us (14), using the same model of the isolated perfused rat liver, we demonstrated an inhibitory effect on lidocaine metabolism. It is for that reason that we consider our negative results valid and in no need for an additional positive control.…”

Section: Discussionmentioning

confidence: 99%

“…This lack of effect of alpha-IFN on the metabolism of lidocaine suggests that alpha-IFN does not inhibit cytochrome P-450 III A4 which is responsible for the metabolism of lidocaine (12)(13)(14). The selective action of IFN on the various subclasses of cytochrome P-450 needs further investigation in order to better define the drugs which mayor may not interact with IFN.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacokinet., 1994, No.2 Lidocaine, which is metabolized by cytochrome P-450 III A 4 (11), is an important local anaesthetic and antiarrhythmic drug extensively in use. It has already been shown that inhibition of the cytochrome P-450 by cimetidine decreased elimination of lidocaine (12,13) and its extraction by the isolated perfused rat liver (14). In this study we investigated the effect of rat alpha-IFN on lidocaine elimination in the whole rat and on lidocaine extraction in the isolated perfused rat liver.…”

Section: Introductionmentioning

confidence: 99%

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Alpha interferon has no effect on lidocaine metabolism in the rat

Melzer

Bardan

Ronen

et al. 1994

Eur. J. Drug Metab. Pharmacokinet.

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Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine elimination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blood was drawn from the arterial catheter for lidocaine determination every 3 min for 20 min. 7 rats were pre-treated with intramuscular rat alpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rats were given saline i.m. The lidocaine elimination rate constant was unchanged, 0.065 min-1 and 0.063 min-1 for the control and IFN groups, respectively. To investigate lidocaine extraction, the isolated perfused rat liver was used. Perfusate samples from the portal and hepatic veins were drawn at 2 min intervals for 20 min, and lidocaine extraction determined. Extraction was determined in two groups of 6 rats each. The first group served as control and these rats were injected with saline only, while in the second group, the rats were pre-treated with rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated perfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded that the rat alpha-IFN affects neither the elimination nor the extraction of lidocaine.

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Vanadate inhibits glucose output from isolated perfused rat liver

et al. 1991

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Previous studies have demonstrated that vanadate ions mimic many of the actions of insulin in in vitro systems. Also, vanadate administered to diabetic hyperglycemic rats lowers their blood glucose levels to normal values. In this study we demonstrate that vanadate inhibits glucose output in the isolated perfused rat liver. Glucose production was suppressed maximally (about 50% to 60%), on addition of extremely low vanadate ion concentrations (0.5 to 1 mumol/L). This concentration is about two log units lower than the vanadate ion concentrations that are required to activate hexose uptake and glucose metabolism in vitro and is within the range of endogenous intracellular vanadium concentration. Insulin had little or no effect in inhibiting hepatic glucose output in this experimental system. The effect of vanadate ions is rapid in onset and is not accompanied by any signs of liver toxicity as assessed by various criteria. In conclusion, the study indicates that (a) vanadate ions inhibits hepatic glucose output, maximally and at extremely low, nontoxic concentrations (ID50 = 0.7 +/- 0.1 mumol/L). (b) The modulation action of the ion is fast and probably occurs at point(s) distal to the insulin receptor itself. (c) The liver participates in the process of maintaining euglycemia in diabetic rats receiving optimal doses of vanadate orally.

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Cimetidine and omeprazole have different effects on hepatic extraction of lidocaine in rats

Cited by 11 publications

References 13 publications

Update on the Use of Metabolic Probes to Quantify Liver Function: Caffeine versus Lidocaine

Update on the Use of Metabolic Probes to Quantify Liver Function: Caffeine versus Lidocaine

Alpha interferon has no effect on lidocaine metabolism in the rat

Vanadate inhibits glucose output from isolated perfused rat liver

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