Clinafloxacin-Theophylline Drug Interaction

Matuschka, Paul R.; Vissing, Richard S

doi:10.1177/106002809502900407

Cited by 11 publications

(6 citation statements)

References 4 publications

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“…Comparison of the structure of clinafloxacin with those of several marketed and experimental quinolone antibiotics suggests a "very high" relative potential for a theophylline interaction. Inhibition of theophylline metabolism was reported in a clinafloxacin clinical study (25). Theophylline concentrations in plasma increased nearly twofold during clinafloxacin therapy compared to those observed prior to clinafloxacin therapy.…”

mentioning

confidence: 83%

Drug Interactions with Clinafloxacin

Randinitis¹,

Alvey²,

Koup³

et al. 2001

Antimicrob Agents Chemother

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Many fluoroquinolone antibiotics are inhibitors of cytochrome P450 enzyme systems and may produce potentially important drug interactions when administered with other drugs. Studies were conducted to determine the effect of clinafloxacin on the pharmacokinetics of theophylline, caffeine, warfarin, and phenytoin, as well as the effect of phenytoin on the pharmacokinetics of clinafloxacin. Concomitant administration of 200 or 400 mg of clinafloxacin reduces mean theophylline clearance by approximately 50 and 70%, respectively, and reduces mean caffeine clearance by 84%. (R)-Warfarin concentrations in plasma during clinafloxacin administration are 32% higher and (S)-warfarin concentrations do not change during clinafloxacin treatment. An observed late pharmacodynamic effect was most likely due to gut flora changes. Phenytoin has no effect on clinafloxacin pharmacokinetics, while phenytoin clearance is 15% lower during clinafloxacin administration.Clinafloxacin is a potent quinolone antibacterial with a broad range of activity that is of potential clinical importance in the management of serious infections, including those caused by many bacteria resistant to a wide variety of other antibiotics (5,6,7,11,16,27). It has been studied primarily in adults hospitalized for the treatment of serious and potentially life-threatening infections, including nosocomial pneumonia, community-acquired pneumonia, febrile neutropenia, complicated intra-abdominal infections, complicated skin and soft tissue infections, endocarditis, and acute gynecologic infections.Clinafloxacin pharmacokinetics in healthy subjects have been reported previously (31). Following administration of 200-and 400-mg twice-daily intravenous doses, the mean values for total body clearance and volume of distribution are approximately 320 ml/min and 156 liters, respectively, and the mean terminal elimination half-life (t 1/2 ) is approximately 5.8 h. Clinafloxacin is approximately 50% bound to plasma protein, independent of concentration. Approximately 50 to 70% of a clinafloxacin dose is excreted unchanged in urine, indicating that renal clearance is the primary route of elimination. Clinafloxacin clearance is correlated to degree of renal function as measured by creatinine clearance (CL CR ). Based on the relationship between clinafloxacin clearance and CL CR , patients with CL CR values of Ͻ40 ml/min should have their daily clinafloxacin dose halved (34).The ability of clinafloxacin to inhibit seven major cytochrome P450 enzymes, CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, was investigated using isoform-selective marker substrates and human liver microsomal preparations (T. F. Woolf and W. F. Trager, personal communication). Clinafloxacin was most effective in inhibiting CYP1A2 with nearly 50% inhibition observed at the 5 M concentration. CYP2A6, CYP2E1, and CYP3A4 were not inhibited even at a clinafloxacin concentration of 125 M. CYP2C19 was 15 and 75% inhibited at 5 and 125 M clinafloxacin concentrations, respectively. A weaker interaction...

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mentioning

confidence: 83%

Drug Interactions with Clinafloxacin

Randinitis¹,

Alvey²,

Koup³

et al. 2001

Antimicrob Agents Chemother

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“…A 600 mg daily dose of ciprofloxacin has been observed to cause an increase in the C max and AUC of theophylline of 17% and 22%, respectively (242). Clinafloxacin (200 mg every 12 h) was reported to produce a more than doubling of serum theophylline concentration in one case report (241). Finally, grepafloxacin (600 mg every day) has been reported to increase the C max of theophylline by 82% and to decrease the total theophylline clearance by about 50% (243).…”

Section: Metal Ion-containing Drugsmentioning

confidence: 98%

“…If this is not feasible, the fluoroquinolone should be administered at least 2 h before or 6 h after the ingestion of the metal ion-containing drug (6,236,240). Theophylline: The metabolic enzyme cytochrome P450 1A2 can be inhibited by several of the fluoroquinolones (ciprofloxacin, clinafloxacin, grepafloxacin), resulting in reduced clearance of theophylline (241,242). This can lead to increased serum theophylline levels and potential toxicity (6,241).…”

Section: Metal Ion-containing Drugsmentioning

confidence: 99%

“…Levofloxacin, moxifloxacin, sparfloxacin and trovafloxacin have not been observed to produce a clinically significant increase in theophylline levels (242,(244)(245)(246)(247)(248). If ciprofloxacin or clinafloxacin is administered to a patient on theophylline, theophylline levels should be monitored and the dosage of theophylline adjusted when necessary (6,241). For concomitant grepafloxacin therapy, the dosage of theophylline should be reduced by 50% and theophylline levels monitored (243).…”

Section: Metal Ion-containing Drugsmentioning

confidence: 99%

See 1 more Smart Citation

The New Fluoroquinolones: A Critical Review

Zhanel

Walkty

Vercaigne

et al. 1999

Canadian Journal of Infectious Diseases and Medical Microbiolog

109

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“…In 1984, Wijnands et al first reported severe clinical adverse effects with the concomitant use of TP and enoxacin, and they found that co-administration of enoxacin markedly increased plasma TP concentrations [11] . Consequently, a series of fluoroquinolones, including ciprofloxacin, tosufloxacin, clinafloxacin, grepafloxacin, and pefloxacin, have been reported to interfere with TP metabolism by inhibiting CYP1A2 activity [12][13][14][15] . Therefore, it is important to evaluate the interaction between ATFX and TP to understand the pharmacokinetics and safety of these drugs.…”

Section: Modulation Of Pharmacokinetics Of Theophylline By Antofloxacmentioning

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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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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Clinafloxacin-Theophylline Drug Interaction

Cited by 11 publications

References 4 publications

Drug Interactions with Clinafloxacin

Drug Interactions with Clinafloxacin

The New Fluoroquinolones: A Critical Review

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

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