A study of the in vitro interaction between lidocaine and premedications using human liver microsomes*

Nagashima, Atsushi; Tanaka, Einosuke; Inomata, Shinichi; Honda, Katsuya; Misawa, Shogo

doi:10.1111/j.1365-2710.2004.00617.x

Cited by 9 publications

(8 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, there is a considerable potential for drug interactions to occur in anesthetic practice. Drug-drug interactions between various classes of compounds have been reported and can be pharmacokinetic and/or pharmacodynamic in nature (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

In vitro binding of lidocaine to liver tissue under the influence of propranolol: Another mechanism of interaction?

Tesseromatis

Kotsiou²,

Tsagataki

et al. 2007

Eur. J. Drug Metabol. Pharmacokinet.

View full text Add to dashboard Cite

The co-administration of lidocaine and propranolol leads to significant drug-drug interactions. Beta-blockers decrease liver perfusion and inhibit the activity of hepatic microsomal lidocaine metabolizing enzymes of the P450_2D subfamily. Hence, there is a resulting reduction in the hepatic breakdown of lidocaine and an increase in its serum concentrations. In this study the ability of propranolol to displace lidocaine from its binding sites in liver tissue has been examined through an in vitro model. Rat liver slices were incubated together with propranolol and/or lidocaine in human serum and the percentage of the bound fraction of lidocaine in the experimental mixture was assessed. The present results indicate that propranolol significantly decreases the binding process of lidocaine in liver tissue. This effect develops only when blood is used as incubation medium and the incubation period lasts 60 min. In conclusion, propranolol can displace lidocaine from liver proteins and therefore the co-administration of the two drugs may increase the free fraction of lidocaine excreted by the liver. However, this result arises from an in virro model and thus further investigation is needed.

show abstract

Section: Introductionmentioning

confidence: 99%

In vitro binding of lidocaine to liver tissue under the influence of propranolol: Another mechanism of interaction?

Tesseromatis

Kotsiou²,

Tsagataki

et al. 2007

Eur. J. Drug Metabol. Pharmacokinet.

View full text Add to dashboard Cite

show abstract

“…Due to the high level of relevant enzymatic activity in the colon, natural polysaccharides are being used in the development of solid dosage forms for colon-specific delivery (38). The potential of the azoreductase activity for colon-specific drug delivery has been also evaluated (13,14,29,30,35,39). Prodrugs, e.g., 5-[4-(2-pyridylaminosulfonyl)phenylazo]-salicylic acid (29) and 5,5′-azodisalicylic acid (30) are used clinically.…”

Section: Discussionmentioning

confidence: 99%

“…The potential of the azoreductase activity for colon-specific drug delivery has been also evaluated (13,14,29,30,35,39). Prodrugs, e.g., 5-[4-(2-pyridylaminosulfonyl)phenylazo]-salicylic acid (29) and 5,5′-azodisalicylic acid (30) are used clinically. The use of water-soluble copolymers for the colon-specific oral delivery of 5-ASA has been proposed by Brown et al (39), and crosslinked (branched) copolymers for the colonic delivery of proteins were introduced by Saffran et al (35).…”

Section: Discussionmentioning

confidence: 99%

“…The eluent was combined with 0.25 ml of HPLC mobile phase solution and filtered through a 0.45 μm nylon membrane filter before HPLC analysis. After sample injection, lidocaine was separated by a C 18 reserved-phase column with a mobile phase of 0.05 M KH 2 PO 4 -acetonitrile (86:14, v/v, pH 4.0) at a flow rate of 1 ml/min and r.t, and detected at 205 nm (30).…”

Section: Hplc Analysis Of 9-ac and Lidocainementioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

et al. 2007

View full text Add to dashboard Cite

Purpose-To quantitate and predict colon-specific 9-aminocamptothecin (9-AC) release from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-9-AC conjugate and its absorption behavior after oral administration in rats.Methods-Drug distribution in the gastrointestinal (GI) tract and the plasma concentration-time profile of 9-AC released from the HPMA copolymer conjugate were predicted using the degradation, transit, and absorption rate constants in cecum. The fate of 9-AC in cecum and liver was measured by in-situ cecum absorption and liver perfusion.Results-Following oral administration of the conjugate, 9-AC was released rapidly in cecum. Based on the pharmacokinetic model, up to 60% of the dose was in the cecum at ∼6 h, and 7% of the dose still remained there at 24 h. The predicted plasma concentration curve for released 9-AC after an oral dose of 3 mg/kg of 9-AC equivalent increased gradually and reached a peak of 98 nM at 7 h, then started decreasing slowly to 16 nM at 24 h. The bioavailability value was estimated as 0.31 after the first-pass elimination.Conclusions-A pharmacokinetic model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition following oral administration of HPMA copolymer-9-AC conjugate in rats.

show abstract

“…Seven different drug substances (Sjödin et al, 2008) were used in this study to cause anesthesia and pain relief. Four of these drugs (ketamine, pancuronium, tiletamine, and zolazepam) are known to be metabolized by P450 enzymes or to affect P450-mediated metabolism (Wong and Bandiera, 1998;Hijazi and Boulieu, 2002;Nagashima et al, 2005). All pigs received identical anesthesia and analgesia in combination with the drugs under investigation, and this makes it possible to compare the data among the groups.…”

Section: Lundahl Et Almentioning

confidence: 99%

In Vivo Investigation in Pigs of Intestinal Absorption, Hepatobiliary Disposition, and Metabolism of the 5α-Reductase Inhibitor Finasteride and the Effects of Coadministered Ketoconazole

Lundahl¹,

Hedeland²,

Bondesson³

et al. 2011

Drug Metabolism and Disposition

View full text Add to dashboard Cite

ABSTRACT:The overall aim of this detailed investigation of the pharmacokinetics (PK) and metabolism of finasteride in pigs was to improve understanding of in vivo PK for this drug and its metabolites. Specific aims were to examine the effects of ketoconazole coadministration on the PK in three plasma compartments (the portal, hepatic, and femoral veins), bile, and urine and to use these data to study in detail the intestinal absorption and the liver extraction ratio and apply a semiphysiological based PK model to the data. The pigs received an intrajejunal dose of finasteride (0.8 mg/kg) either alone (n ‫؍‬ 5) or together with ketoconazole (10 mg/kg) (n ‫؍‬ 5) or an intravenous dose (0.2 mg/kg) (n ‫؍‬ 3). Plasma, bile, and urine (collected from 0 to 6 h) were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry. Ketoconazole increased the bioavailability of finasteride from 0.36 ؎ 0.23 to 0.91 ؎ 0.1 (p < 0.05) and the terminal half-life from 1.6 ؎ 0.4 to 4.0 ؎ 1.1 h (p < 0.05). From deconvolution, it was found that the absorption rate from the intestine to the portal vein was rapid, and the product of the fraction absorbed and the fraction that escaped gut wall metabolism was high (f a ⅐ F G ϳ1). Interestingly, the apparent absorption rate constant (k a ) to the femoral vein was lower than that to the portal vein, probably because of binding and distribution within the liver. The liver extraction ratio was time-dependent and varied with the two routes of administration. After intrajejunal administration, from 1 to 6 h, the liver extraction ratio was significantly (p < 0.05) reduced by ketoconazole treatment from intermediate (0.41 ؎ 0.21) to low (0.21 ؎ 0.10).

show abstract

A study of the in vitro interaction between lidocaine and premedications using human liver microsomes*

Abstract: These results show that the interactions between lidocaine and midazolam and thiamylal are of potential toxicological and clinical significance.

Cited by 9 publications

References 18 publications

In vitro binding of lidocaine to liver tissue under the influence of propranolol: Another mechanism of interaction?

In vitro binding of lidocaine to liver tissue under the influence of propranolol: Another mechanism of interaction?

Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

In Vivo Investigation in Pigs of Intestinal Absorption, Hepatobiliary Disposition, and Metabolism of the 5α-Reductase Inhibitor Finasteride and the Effects of Coadministered Ketoconazole

Contact Info

Product

Resources

About