Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2

Kinzig‐Schippers, Martina; Fuhr, Uwe; Zaigler, M; Dammeyer, Jörg; Rüsing, Guido; Labedzki, Andreas; Bulitta, Jürgen B.; Sörgel, Fritz

doi:10.1016/s0009-9236(99)70105-0

Cited by 37 publications

(15 citation statements)

References 40 publications

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“…This was in contrast to the findings at steady state (d 5) that the co-administration of ATFX on d 1 did not alter the plasma concentrations of TP or the urinary excretion of TP metabolites ( Figure 1 and Table 1), although the ATFX concentrations in plasma on d 1 were higher than those on d 5 Table 2). Similar phenomena were found for the effects of tosufloxacin on TP plasma concentrations and the effects of enoxacin on caffeine concentrations [20,27] . The in vitro results using human liver microsomes showed that ATFX is a weak reversible inhibitor of CYP1A2, but ATFX appears to be a clinically relevant inhibitor.…”

Section: Discussionsupporting

confidence: 78%

“…The non-renal clearance (Cl nr ) was designed to be Cl/F-Cl r . Analysis of the differences between the pharmacokinetic parameters of drug alone and the combination of drugs was handled as an equivalence problem [20] . Comparison of pharmacokinetic parameters was carried out with analysis of variance (ANOVA)-based 90% confidence intervals (CI) after log-transformation.…”

Section: Discussionmentioning

confidence: 99%

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Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino-fluoroquinolone, in humans

Liu

Pan

Liu³

et al. 2011

Acta Pharmacol Sin

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Aim: To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro. Methods: A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylline (100 mg twice a day and morning dose 200 mg on d 1 and 5), or theophylline plus antofloxacin. The plasma and urinary pharmacokinetics of antofloxacin and theophylline were characterized after the first and last dose. The effect of antofloxacin on theophylline metabolism was also investigated in pooled human liver microsomes. Results: The 5-day treatment with antofloxacin significantly increased the area of the plasma concentration-time curve and peak plasma concentration of theophylline, accompanied by a decrease in the excretion of theophylline metabolites. On the contrary, theophylline did not affect the pharmacokinetics of antofloxacin. In vitro studies using pooled human hepatic microsomes demonstrated that antofloxacin was a weak reversible and mechanism-based inhibitor of CYP1A2. The clinical interaction between theophylline and antofloxacin was further validated by the in vitro results. Conclusion:The results showed that antofloxacin increases the plasma theophylline concentration, partly by acting as a mechanismbased inhibitor of CYP1A2.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino-fluoroquinolone, in humans

Liu

Pan

Liu³

et al. 2011

Acta Pharmacol Sin

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“…Since they all induce CYP1A2 enzymes in humans, the mechanism for the increased caffeine metabolism is increased amounts of CYP1A1 and CYP1A2 in the liver. In agreement with this notion, other CYP1A enzyme inducing xenobiotics, like omeprazol, cause a similar type of effect (Nousbaum et al, 1994;Kinizig-Schippes et al, 1999). Secondly, a prolonged half-life of caffeine is observed when the catalysis via CYP1A2 is reduced, either due to inhibition by the si-multaneous presence of specific CYP1A2 xenobiotic inhibitors or due to reduced amount of the enzyme being present in the liver (Kalow, 1985).…”

Section: Metabolism In the Adult Human Beingmentioning

confidence: 85%

Intake of caffeine and other methylxanthines during pregnancy and risk for adverse effects in pregnant women and their foetuses

Andersson¹,

Hallström²,

Kihlman³

2005

TemaNord

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“…A number of the quinolones have been found to reduce the hepatic metabolism of coadministered drugs such as the xanthines theophylline and caffeine [171][172][173][174][175][176][177][178][179][180] (Table 9.2). In contrast to the absorption interactions with multivalent cations, which appear to be generalizable to the entire quinolone drug class, differences do exist between individual quinolones in their propensity to inhibit hepatic xanthine metabolism.…”

Section: Metabolism Interactionsmentioning

confidence: 99%

Quinolones

Guay¹

2011

Drug Interactions in Infectious Diseases

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Fluoroquinolone (FQ) antimicrobials are among the most commonly used agents in the outpatient and institutional patient care environments. Due to this high frequency of utilization, the potential for deleterious drug-drug interactions with nonantimicrobials is also high. The majority of interactions with the FQs involve deleterious effects on the FQ component. These are also the most clinically-important interactions with these agents. Multivalent cations such as Mg , and other minerals as well as drugs such as sucralfate, lanthanum, sevelamer, and didanosine (the cation-supplemented version of the latter) can substantially reduce FQ bioavailability, leading the subtherapeutic drug concentrations at the infection site and clinical failure. Separation of dose administrations may or may not reduce the magnitude of these interactions. Ciprofloxacin, norfloxacin, and two experimental FQs in clinical trials (pazufloxacin and prulifloxacin) act as moderate cytochrome P450 enzyme inhibitors and may increase serum concentrations of theophylline and caffeine. Warfarin pharmacodynamics are variably affected by the FQs. The pharmacodynamic interactions between NSAIDs and FQs are only relevant if fenbufen is used concurrently with enoxacin or, possibly, prulifloxacin. Caution is warranted if sparfloxacin or moxifloxacin is used concurrently with other medications prolonging the QTc interval or if patients have other risk factors for prolongation of the QTc interval (e.g. abnormal QTc interval pre-treatment, electrolyte abnormalities, use of starvation-liquid diets, or history of heart disease). Fluoroquinolone antimicrobials can be used effectively and safely in the vast majority of patients if the clinician remembers those few drug-drug interactions that are clinically-important.

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Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2

Abstract: Enoxacin and to a lesser extent pefloxacin may cause clinically relevant interactions with further CYP1A2 substrates. The data suggest that the pefloxacin interaction is partly mediated by its major metabolite norfloxacin.

Cited by 37 publications

References 40 publications

Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino-fluoroquinolone, in humans

Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino-fluoroquinolone, in humans

Intake of caffeine and other methylxanthines during pregnancy and risk for adverse effects in pregnant women and their foetuses

Quinolones

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