Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition

Barnett, Gene; Segura, Jordi; Torre, Rafael de la; Carbó, Marcel·lí

doi:10.1007/bf02657060

Cited by 19 publications

(7 citation statements)

References 24 publications

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“…Therefore, we have proposed that position 3 of the piperazinelike ring at position 7 of the quinolone molecule plays an important role in the interaction between theophylline and quinolones, since the substituent group at the 1-nitrogen atom of the quinolone molecule is not as important in the inhibition of caffeine metabolism (1).…”

Section: Discussionmentioning

confidence: 99%

Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients

Takagi

Yamaki

Nadai

et al. 1991

Antimicrob Agents Chemother

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Recently, it has become evident that some quinolones affect the processing of theophylline in the human system. The effect of a new quinolone, sparfloxacin, on the pharmacokinetics and metabolism of theophyUine was investigated in six asthmatic patients receiving chronic theophylline therapy (a sustained-release theophylline tablet formulation of 200 to 300 mg twice daily at 12-h intervals). To these patients, sparfloxacin (200 mg once daily) was coadministered for 1 week. Plasma and urine samples were analyzed by highperformance liquid chromatography for theophyiline and its metabolites. Plasma theophyiline concentrationtime curves and the urinary excretion of theophyline and its major metabolites before and after coadministration of sparfloxacin were compared. The total body clearance of theophylline after coadministration of sparfloxacin, 42.81 + 6.64 mI/h/kg (mean ± standard error of the mean), was not significantly different from that after the administration of theophylline alone, 47.11 ± 7.61 mW/kg. Also, no significant change in the urinary excretion of theophylline and its metabolites was observed for subjects receiving or not receiving sparfloxacin. These findings indicate that a once-daily dose of 200 mg of sparfioxacin has no significant effect on the pharmacokinetics and metabolism of theophylline and that it would be safe to coadminister this quinolone to asthmatic patients receiving chronic theophylline therapy.Theophylline is widely used in the treatment of patients with reversible obstructive airway diseases. In treating asthma, however, theophylline is commonly prescribed in combination with various other drugs. Many articles have been published on the interactions of theophylline with other drugs (13,15,17,18,31). Some quinolone antimicrobial drugs (ciprofloxacin, enoxacin, pefloxacin, and tosufloxacin), when coadministered with theophylline, may create clinical problems due to an inhibition of theophylline clearance, thus increasing the risk of the development of serious side effects (7,8,22,24,29,30).The mechanism of the decrease in theophylline clearance due to quinolones has generally been considered to be an inhibition of theophylline metabolism. However, the precise mechanism of the interaction between theophylline and quinolones is not yet fully understood. Therefore, interest remains in determining the pharmacokinetic interactions between theophylline and quinolones.A large number of new quinolone antimicrobial drugs with broad-spectrum activity have been developed in the past few years. Sparfloxacin (Fig. 1) has broad antibacterial activity against both gram-positive and gram-negative bacteria. This study was conducted as part of a program directed to the development of guidelines for the safe use of quinolone drugs in combination with theophylline in asthmatic patients. We investigated the possibility that multiple oral doses of sparfloxacin may affect the pharmacokinetics of theophylline in asthmatic patients receiving chronic theophylline therapy. MATERIALS AND METHODSPatients. Six...

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Section: Discussionmentioning

confidence: 99%

Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients

Takagi

Yamaki

Nadai

et al. 1991

Antimicrob Agents Chemother

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“…The quinolones that inhibit theophylline metabolism also inhibit caffeine metabolism (Barnett et al 1990;Harder et al 1988;Healy et al 1989;Radandt et al 1992;Staib et al 1987). Enoxacin reduces caffeine clearance by approximately 80% and was reported to be associated with increased nausea and vomiting (Peloquin et al 1989).…”

Section: Methylxanthinesmentioning

confidence: 99%

Pharmacokinetic Drug Interactions with Antimicrobial Agents

Gillum

Israel

Polk

1993

Clinical Pharmacokinetics

129

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As new classes of antimicrobial drugs have become available, and new uses found for older drugs, pharmacokinetic drug interactions with antimicrobials have become more common. Macrolides, fluoroquinolones, rifamycins, azoles and other agents can interact adversely with commonly used drugs, usually by altering their hepatic metabolism. The mechanisms by which antimicrobial agents alter the biotransformation of other drugs is increasingly understood to reflect inhibition or induction of specific cytochrome P450 enzymes. Macrolides inhibit cytochrome P450IIIA4 (CYP3A4), which appears to be the most common metabolic enzyme in the human liver and is involved in the metabolism of many drugs, including cyclosporin, warfarin and terfenadine. Some quinolones preferentially inhibit CYP1A2, which is partially responsible for methylxanthine metabolism. Azoles appear to be broad spectrum inhibitors of cytochromes P450. Within each of these antibiotic classes, there is a rank order of inhibitory potency towards specific cytochrome P450 enzymes. By contrast, rifampicin (rifampin) and rifabutin induce several cytochromes P450, including CYP3A4, and hence can enhance the metabolism of many other drugs. By using in vitro preparations of human enzymes it is increasingly possible to predict those antibiotics that will adversely affect the metabolism of other drugs. In addition, between-patient variability in frequency of interaction may relate to differences in the activities of these enzymes. Although the mechanisms and scope of these interactions are becoming well characterised, the remaining challenge is how to best inform the clinician so that the undesirable consequences of interactions may be prevented.

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“…Interactions between quinolones and caffeine are less well documented, but in vivo studies in healthy volunteers and in vitro studies using human liver microsomes have indicated a similar pattern of inhibition to that seen with theophylline (Barnett et al 1990;Fuhr et al 1990a,b, unpublished data;Harder et al 1989;Staib et al 1990). Thus, clearance of caffeine in healthy volunteers was decreased by concurrent administration of enoxacin (Mahr et al 1990b;Peloquin et al 1989;Staib et al 1987), ciprofloxacin (Harder et al 1989Staib et al 1987;Stille et al 1987) or pefloxacin (Mahr et al 1990b), whereas norfloxacin (Carbo et al 1989;Harder et al 1989), fleroxacin (Patel et al 1990), or ofloxacin (Harder et al 1989Staib et al 1987;Stille et al 1987) showed a lesser, or no, effect.…”

mentioning

confidence: 73%

Effects of Temafloxacin and Ciprofloxacin on the Pharmacokinetics of Caffeine†

Mahr

Sörgel

Granneman

et al. 1992

Clinical Pharmacokinetics

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A number of quinolone antibacterial agents, particularly enoxacin, pefloxacin, pipemidic acid and ciprofloxacin, are known to decrease the clearance of methylxanthines. The effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine were therefore compared in a 3-way crossover study in 12 healthy young volunteers. Each volunteer received 183mg once-daily doses of caffeine in conjunction with twice-daily placebo, temafloxacin 600mg and ciprofloxacin 750mg in 3 separate phases according to a randomised sequence.A doubling of the area under the plasma concentration-time curve (77.8 vs 31.8 mgfL· h) and terminal-phase half-life (9.7 vs 4.5h) of caffeine were observed in the presence of ciprofloxacin. The magnitude of the reduction in the intrinsic clearance of caffeine produced by ciprofloxacin was greater than that described in the literature for ciprofloxacin and theophylline. This may partly be explained by intertrial differences in dosage and study design.Coadministration oftemafloxacin did not have any effect on the pharmacokinetics of caffeine, confirming results of other studies suggesting that this agent does not affect methylxanthine clearance. Accordingly, it appears that restriction of caffeine intake during temafloxacin therapy is not necessary.

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Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition

Cited by 19 publications

References 24 publications

Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients

Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients

Pharmacokinetic Drug Interactions with Antimicrobial Agents

Effects of Temafloxacin and Ciprofloxacin on the Pharmacokinetics of Caffeine†

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