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The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects.
Author(s) -
Batty KT,
Davis TM,
Ilett KF,
Dusci LJ,
Langton SR
Publication year - 1995
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1995.tb04453.x
Subject(s) - theophylline , cyp1a2 , pharmacokinetics , pharmacology , ciprofloxacin , oral administration , demethylation , medicine , cyp3a4 , drug interaction , chemistry , endocrinology , metabolism , cytochrome p450 , biochemistry , antibiotics , gene expression , dna methylation , gene
1. The mechanism of the interaction between ciprofloxacin and theophylline was investigated in nine healthy subjects. 2. Subjects were given a single oral dose of theophylline (3.4 mg kg‐1), before and after 60 h of ciprofloxacin therapy at a dose of 500 mg twice daily. 3. Ciprofloxacin reduced the oral clearance of theophylline by 19% (‐7.73 +/‐ 6.42 ml kg‐1 h‐1 (95% confidence limits ‐12.66, ‐2.79)). Some subjects (group A, n = 4) showed little decrease in clearance (mean 4.4%; ‐1.6 +/‐ 0.7 ml kg‐1 h‐1 (‐2.6, 0.5)), whereas others (group B, n = 5) showed a marked decrease (mean 30%; ‐12.7 +/‐ 3.7 ml kg‐1 h‐1 (‐ 17.2, ‐8.1)). 4. Comparing groups A and B, the decrease in oral clearance of theophylline in group B could not be ascribed to differences in the AUC of ciprofloxacin. Group A subjects showed only slight inhibition of 1‐demethylation (‐12.8 +/‐ 5.5% (‐21.5, ‐4.0)), while group B subjects showed a significantly greater inhibition of 1‐ demethylation (‐49.9 +/‐ 9.8% (‐62.1, ‐37.7)), 3‐demethylation (‐44.8 +/‐ 8.6% (‐55.4, ‐34.1)) and 8‐hydroxylation (‐27.0 +/‐ 3.7% (‐31.6, ‐ 22.4)). 5. The results suggest that inter‐individual variability in the inhibition of theophylline metabolism by ciprofloxacin can be attributed to inter‐individual differences in the level of CYP1A2 expression and/or in the degree of inhibition of hepatic CYP1A2 and CYP3A4. 6. The interaction between ciprofloxacin and theophylline can be clinically significant.(ABSTRACT TRUNCATED AT 250 WORDS)