Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin.

Milne, Robert; Coulthard, Kingsley; Nation, Roger L.; Penna, A. C.; Roberts, G. W.; Sansom, LN

doi:10.1111/j.1365-2125.1988.tb05285.x

Cited by 20 publications

(6 citation statements)

References 5 publications

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“…It appears that there is a discrepancy be tween the findings of the present study and a previous report which had showed that the clearance of a single dose of phenytoin was unaffected when it was given to animals which had previously been treated for 4.5 days with erythromycin [29]. This contradic tion may be due to the different experimental protocols followed, since in this study the ani mals were pretreated for 4 days with pheny toin to induce cytochrome P-450 before the macrolides were administered.…”

Section: Discussioncontrasting

confidence: 56%

Pharmacokinetic Interactions between Erythromycin, Clarithromycin, Roxithromycin and Phenytoin in the Rat

Al-Humayyd

1997

Chemotherapy

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The effects of the macrolide antibiotics, erythromycin, clarithromycin and roxithromycin, on the pharmacokinetic profile of phenytoin were studied in rats. Animals were injected with phenytoin (100 mg/kg, i.p.) daily for 4 days and then they were given phenytoin (20 mg/kg, i.p.) alone or the same dose of phenytoin together with erythromycin (50 mg/kg, i.p.), clarithromycin (50 mg/kg, i.p.) or roxithromycin (50 mg/kg, i.p.). In another set of experiments, the same protocol was followed except that erythromycin (100 mg/kg), clarithromycin (100 mg/kg) and roxithromycin (100 mg/kg) were given by the oral route. The concentrations of phenytoin in plasma were determined using a high-performance liquid chromatographic method. The area under the curve the maximum plasma concentration and the elimination half-life (t_½) of phenytoin were significantly (p < 0.05) increased by the macrolides. In addition, the macrolides significantly (p < 0.05) reduced the level of hepatic cytochrome P-450 in the rats. These results suggest that a potentially harmful drug-drug interaction may occur if phenytoin is administered concurrently with erythromycin, clarithromycin or roxithromycin.

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Section: Discussioncontrasting

confidence: 56%

Pharmacokinetic Interactions between Erythromycin, Clarithromycin, Roxithromycin and Phenytoin in the Rat

Al-Humayyd

1997

Chemotherapy

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“…Finally, several studies found that ERY exhibited no effect on the co-administered agents oxcarbazepine [227], phenytoine [228], or tiagabin [229]. …”

Section: Resultsmentioning

confidence: 99%

“…When phenytoin was administered to patients also receiving josamycin, no PK changes were observed compared to monotherapy [ 217 ]. Finally, several studies found that ERY exhibited no effect on the co-administered agents oxcarbazepine [ 227 ], phenytoine [ 228 ], or tiagabin [ 229 ].…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

et al. 2011

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Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.

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“…Available evidence from interaction studies indicates that β‐adrenoceptor antagonists [110], dextropropoxyphene [111], diltiazem [112], enoxacin [113], erythromycin [81, 114], metronidazole [115], olanzapine [116] and omeprazole [117, 118] are all unlikely to inhibit CYP2C9 activity in vivo .…”

Section: Factors Affecting Cyp2c9 Activitymentioning

confidence: 99%

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

Miners

Birkett

1998

Brit J Clinical Pharma

729

533

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Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs. CYP2C9 activity in vivo is inducible by rifampicin. Evidence suggests that CYP2C9 substrates may also be induced variably by carbamazepine, ethanol and phenobarbitone. Apart from the mutual competitive inhibition which may occur between alternate substrates, numerous other drugs have been shown to inhibit CYP2C9 activity in vivo and/or in vitro. Clinically significant inhibition may occur with coadministration of amiodarone, fluconazole, phenylbutazone, sulphinpyrazone, sulphaphenazole and certain other sulphonamides. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino acid residues 144 (Arg144Cys) and 359 (Ile359Leu) of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, although the frequency of this allele is relatively low. Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. Individualisation of dose is essential for those CYP2C9 substrates with a narrow therapeutic index.

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Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin.

Cited by 20 publications

References 5 publications

Pharmacokinetic Interactions between Erythromycin, Clarithromycin, Roxithromycin and Phenytoin in the Rat

Pharmacokinetic Interactions between Erythromycin, Clarithromycin, Roxithromycin and Phenytoin in the Rat

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

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