Pharmacogenetic differences in the inhibitory effect of cimetidine on the metabolism of antipyrine

Gachályi, B; A, Vas; Csillag, Kinga; Nagy, Bernadett; Kocsis, F; Káldor, A

doi:10.1007/bf00606641

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…From the AP metabolite data it is evident that the cumulative excretion and CLm of NORA were significantly lower in the presence of cimetidine (Table lb). These data on AP metabolism during cimetidine coadministration are similar to those from many previous reports (Teunissen et al, 1985;Gachalyi et al, 1987;Labs, 1988). Recently cimetidine pretreatment was reported to decrease the elimination rate of TMO when incubated with rat liver microsomes (Tanaka & Misawa, 1985;Tanaka et al, 1986b).…”

Section: Discussionsupporting

confidence: 90%

The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

Tanaka¹,

Nakamura²

1989

Brit J Clinical Pharma

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The effect of pretreatment for 7 days with either roxatidine acetate 75 mg twice daily or cimetidine 200 mg four times daily on the kinetics of antipyrine (AP), trimethadione (TMO) and indocyanine green (ICG) was studied in seven healthy, male, nonsmoking subjects. After pretreatment with cimetidine, the plasma clearances (CL) of AP and TMO were significantly lower and the elimination half-life (t½) of AP was significantly increased.The volumes of distribution (V) of AP and TMO were not affected. After roxatidine acetate, the pharmacokinetics of AP and TMO were unchanged. The cumulative renal excretion (% dose) and formation clearance of 3-hydroxymethyl-3-nor-antipyrine (NORA) were lowered by cimetidine treatment, but not following the administration of roxatidine acetate. ICG clearance was not changed significantly by either pretreatment. The results of this study show that roxatidine acetate does not impair the metabolism of three model substrates used to assess hepatic drug clearance.

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Section: Discussionsupporting

confidence: 90%

The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

Tanaka¹,

Nakamura²

1989

Brit J Clinical Pharma

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“…Similar findings were reported by Dossing et al (1993). In contrast, Gasachalyi et al, (1987) found that cimetidine decreased only the partial clearance of norantipyrine. Back et al (1988) reported, that cimetidine caused at least a 30% decrease in the clearance of each of the metabolites, but was statistically significant only for HMA.…”

supporting

confidence: 85%

“…The latter finding may perhaps be due to the increase in the apparent volume of distribution. A similar increase in the distribution volume of antipyrine in the presence of cimetidine was found by Gasachalyi et al (1987).…”

supporting

confidence: 78%

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The effect of cimetidine on antipyrine metabolism in calves

Janus

Suszycka

1997

Vet Pharm & Therapeutics

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“…It has been shown that such treatments are of sufficient duration to inhibit liver microsome activity (Cimetidine: Jackson et al, 1981;Grygiel et al, 1984;Jonkman and Upton, 1984;Cusack et al, 1985 ;Gachalyi et al, 1987. Troleandomycin: Weinberger et al, 1976Lavarenne et af., 1981 ;Jonkman and Upton, 1984;Brazier et at., 1980;Ketoconazole: Brown et af., 1985).…”

Section: Protocolmentioning

confidence: 99%

Application of Theophylline Metabolite Assays to the Exploration of Liver Microsome Oxidative Function in Man

Naline

Sanceaume

Pays

et al. 1988

Fundamemntal Clinical Pharma

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The effects on theophylline oxidative metabolism of 3 inhibitors of liver microsome activity--cimetidine, troleandomycin and ketoconazole--were investigated in 6 healthy volunteers. The 3 compounds increased plasma theophylline half-life by 73.6 +/- 15.6% (P less than 0.01), 107.8 +/- 9.7% (P less than 0.001) and 21.7 +/- 6.8% (P less than 0.02), respectively, and reduced plasma theophylline clearance by 38.3 +/- 4.8% (P less than 0.001), 51.4 +/- 2.4% (P less than 0.001), and 8.9 +/- 7.8% (NS), respectively. Troleandomycin inhibited to the same extent the 2 theophylline metabolism pathways: N-demethylation resulting in the formation of 1-methyluric acid (1-MU) and 3-methylxanthine (3-MX), and 8-hydroxylation resulting in the formation of 1,3-dimethyluric acid (1,3-DMU). The production clearances of these metabolites were almost equally depressed by 60.2 +/- 3.9%, 60.2 +/- 2.1%, and 51.7 +/- 4.5%, respectively. Cimetidine predominantly inhibited the N-demethylation pathway; the production clearances of 1-MU and 3-MX were depressed by 58.5 +/- 4.0% and 57.5 +/- 4.1% (P less than 0.001), respectively, whereas the production clearance of 1,3-DMU was depressed by 38.3 +/- 6.1% (P less than 0.001). Ketoconazole had no significant effect on the produciton clearances of theophylline metabolites. Measurement of theophylline metabolite formation clearances might be a useful test to explore liver microsome oxidative function.

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Pharmacogenetic differences in the inhibitory effect of cimetidine on the metabolism of antipyrine

Cited by 7 publications

References 20 publications

The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

The effect of roxatidine acetate and cimetidine on hepatic drug clearance assessed by simultaneous administration of three model substrates.

The effect of cimetidine on antipyrine metabolism in calves

Application of Theophylline Metabolite Assays to the Exploration of Liver Microsome Oxidative Function in Man

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