Effect of temafloxacin on the pharmacokinetics of theophylline

Ruff, F; Santais, M. C.; Callens, E.; Chauvin, Jean‐Paul; Hazebroucq, J.

doi:10.1016/0002-9343(91)90315-o

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…Enoxacin is reported to be the most potent of the quinolone antibiotics in inhibiting theophylline metabolism (38). Theophylline concentrations in plasma are more than doubled and clearance is reduced more than 60% when administered with enoxacin.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

Drug Interactions with Clinafloxacin

Randinitis¹,

Alvey²,

Koup³

et al. 2001

Antimicrob Agents Chemother

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“…Previous studies have examined the potential for drug interactions between clarithromycin and theophylline, carbamazepine, and terfenadine (8,23,24). Results of these studies have shown statistically significant increases in concentrations of theophylline, …”

Section: Discussionmentioning

confidence: 99%

“…During period 1, 7-ml blood samples for determination of omeprazole concentrations in plasma were obtained prior to dosing (zero hour) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 h after dosing on day 6. During periods 2 and 3, two 7-ml blood samples (one for omeprazole in plasma and one for clarithromycin and 14-(R)-hydroxyclarithromycin in plasma) were obtained prior to (zero hour) and 0.5, 1, 1.5, 2, 3, 4,6,8,12,16,24,30, and 36 h after the administration of omeprazole and clarithromycin on day 6. In addition, a 7-ml blood sample was obtained on day 5 of periods 2 and 3 at the time of gastric tissue sample collection for plasma clarithromycin and 14-(R)-hydroxyclarithromycin concentrations.…”

Section: Methodsmentioning

confidence: 99%

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state

Gustavson

Kaiser

Edmonds

et al. 1995

Antimicrob Agents Chemother

118

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This study was conducted to determine (i) the effect of omeprazole on steady-state concentrations of clarithromycin and 14-(R)-hydroxyclarithromycin in plasma and gastric mucosa, (ii) the effect of clarithromycin on steady-state concentrations of omeprazole in plasma, and (iii) the effect of clarithromycin on the suppression of gastric acid secretion by omeprazole. Twenty healthy, Helicobacter pylori-negative male subjects completed this three-period, double-blind, randomized crossover study. In period 1, all subjects received 40 mg of omeprazole each morning for 6 days. Twenty-four-hour gastric pH monitoring took place on days ؊1 and 6. Pharmacokinetic sampling took place on day 6. In periods 2 and 3, subjects were randomly assigned to receive either 40 mg of omeprazole or omeprazole placebo daily for 6 days plus clarithromycin (500 mg) every 8 h for 5 days with a single 500-mg dose on day 6. Gastric tissue and mucus samples were obtained via endoscopy on day 5. Gastric pH monitoring and pharmacokinetic sampling took place on day 6. Two-week washout intervals separated the three study periods. Clarithromycin increased mean omeprazole area under the concentration-time curve from 0 to 24 h from 3.3 ؎ 2.0 to 6.3 ؎ 4.5 g ⅐ h/ml (P < 0.05) and harmonic mean half-life from 1.2 to 1.6 h (P < 0.05) but did not significantly alter the effect of omeprazole on gastric pH. Mean clarithromycin area under the concentration-time curve from 0 to 8 h increased from 22.9 ؎ 5.5 (placebo) to 26.4 ؎ 5.7 g ⅐ h/ml (omeprazole) (P < 0.05) when clarithromycin was administered with omeprazole. Analysis of variance revealed that mean concentrations of clarithromycin in tissue and mucus were statistically significantly higher when clarithromycin was given with omeprazole than when clarithromycin was given with placebo (P < 0.001). Mean maximum observed concentrations of clarithromycin in the gastric fundus increased from 20.8 ؎ 7.6 (placebo) to 24.3 ؎ 6.4 g/g (omeprazole), and those in the gastric mucus increased from 4.2 ؎ 7.7 (placebo) to 39.3 ؎ 32.8 g/g (omeprazole). Similar increases were observed for the 14-(R)-hydroxyclarithromycin. These results show that omeprazole increases concentrations of clarithromycin in gastric tissue and mucus and may provide a mechanism for synergy between clarithromycin and omeprazole that explains the excellent eradication of H. pylori seen in clinical trials.Helicobacter pylori infection has been associated with gastritis, duodenal ulcers, gastric ulcers, and nonulcer dyspepsia. Approximately 85 to 100% of all duodenal ulcers and 70 to 90% of all gastric ulcers are associated with H. pylori infection in the stomach (19). Evidence suggests that eradication of H. pylori is associated with faster healing and a significant decrease in peptic ulcer recurrence (18). Previous studies have demonstrated the susceptibility of H. pylori to various antibiotics or antiulcer agents (2, 15, 16). However, to date no single agent has consistently displayed the capability to eradicate H. pylori from the gastric and duod...

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“…Roxithromycin [215] prolongs the tY2 of theophylline by 8%. [215] However, it has been shown that josamycin, [145,148,236] midecamycin acetate (miocamycin), [150,151] midecamycin [149] and spiramycin [152] have no influence on the pharmacokinetic profile of theophylline. Similarly, amongst the quinolones, pipemidic acid [137] and enoxacin [139,140,146,199,237] decrease the clearance of theophylline markedly by 43 to 73%, while ciprofloxacin [135,139,197] and pefloxacin [139,197] reduce this parameter by approximately 30%.…”

Section: Enzyme Inhibitionmentioning

confidence: 99%

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Tröger

Meyer

1995

Clinical Pharmacokinetics

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Theophylline has been widely used as a bronchodilatory drug for the treatment of neonatal apnoea in premature newborns and patients with obstructive airways disease. The development of analytical equipment and procedures to determine the systemic concentration of theophylline renders it possible to improve the effectiveness of theophylline therapy and reduce the incidence of toxic and adverse effects. Since the beginning of the 1970s, endogenous and exogenous factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal preparation procedure, nutritional habits, pregnancy, gender, smoking and, to a lesser extent, biorhythms), influencing nearly all parameters of theophylline pharmacokinetics have been described. Drug absorption depends on galenic formulation, drug delivery, nutritional habits and the chemical derivatives used. The mean plasma protein binding rates depend on the method of plasma protein determination: acidic blood pH values and advanced age may result in reduced plasma proteins. The volume of distribution depends primarily on age; it is 2-fold greater in newborns than in adults. Furthermore, changes in blood pH values, the plasma protein content and the administration of concomitant drugs may vary this parameter. Biotransformation is the most clinically important pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450 system appear to be responsible for the N-methylation and 8-hydroxylation of the drug. Age and concomitant disease are the major endogenous effectors influencing biotransformation of theophylline, whereas biorhythms, gender and pregnancy are of lesser importance. Exogenous factors, such as concomitantly administered drugs, smoking and nutritional factors, affect biotransformation by inducing or inhibiting the metabolising enzymes. Because of intra- and interindividual variability in the pharmacokinetics of theophylline, which may be increased by the presence of endogenous and/or exogenous effectors, it is necessary to supervise theophylline therapy by therapeutic drug monitoring if target concentrations are to be achieved.

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Effect of temafloxacin on the pharmacokinetics of theophylline

Cited by 7 publications

References 20 publications

Drug Interactions with Clinafloxacin

Drug Interactions with Clinafloxacin

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

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