Comparative studies on interaction between theophylline and quinolones.
A comparative study of the pharmacokinetic and metabolic interactions between theophylline and a newly developed quinolone, T-3262, was carried out under steady-state conditions in seven healthy male volunteers, using enoxacin as the reference drug. A sustained-release theophylline formulation (200 mg twice daily) was given as monotherapy and coadministered with T-3262 (150 mg three times a day) or enoxacin (200 mg three times a day). The total and free concentrations of theophylline in the plasma and the excreted concentration of theophylline and its metabolites in the urine were measured by a high-performance liquid chromatography method. The mean steady-state plasma theophylline concentration significantly increased by approximately 1.5-fold and threefold after coadministration of T-3262 and enoxacin, respectively. In both cases, a significant decrease in the total body clearance was found for T-3262 (34%) and enoxacin (63%), but the plasma protein binding of theophylline remained unchanged. There was a significant increase in urinary theophylline and a decrease in urinary 3-methylxanthine after coadministration of T-3262 or enoxacin. The degree of change in the steady-state plasma theophylline concentration as a result of coadministration of T-3262 was small compared to that of enoxacin. A decrease in the total body clearance in the case of coadministration of a quinolone probably resulted from inhibition of the 1-demethylation metabolic pathway.
Takagi
K
K
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hasegawa
T
T
Ogura
Y
Y
Suzuki
R
R
Yamaki
K
K
Watanabe
T
T
Kitazawa
S
S
Satake
T
T
D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D004347:Drug Interactions; D015365:Enoxacin / Q000493:pharmacokinetics; D024841:Fluoroquinolones; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D009287:Naphthyridines; D009994:Osmolar Concentration; D011804:Quinolines / Q000493:pharmacokinetics*; D013806:Theophylline / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D014556:Urine / Q000032:analysis
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D011804:Quinolines; D015365:Enoxacin; D013806:Theophylline; C055185:tosufloxacin