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. 1995 Sep;39(9):2138–2140. doi: 10.1128/aac.39.9.2138

Influence of a newly developed quinolone, T-3761, on pharmacokinetics of theophylline in rats.

T Hasegawa 1, M Nadai 1, S Haghgoo 1, K Yamaki 1, K Takagi 1, T Nabeshima 1
PMCID: PMC162897  PMID: 8540732

Abstract

The effect of a new quinolone, T-3761, on the pharmacokinetics and metabolism of theophylline was investigated with rats. T-3761 at a high dose (20 mg/kg of body weight) was injected intravenously 10 min before an intravenous administration of theophylline (10 mg/kg). The presence of T-3761 slightly delayed the disappearance of theophylline from plasma. Parameters related to the pharmacokinetic interaction between theophylline and T-3761 were estimated by noncompartmental methods. A significant decrease (approximately 25%) in the systemic clearance of theophylline was observed in the presence of T-3761. However, no significant changes between the control group and the T-3761-treated groups in the volume of distribution at a steady state were observed. Pretreatment with T-3761 increased the urinary excretion of unchanged theophylline (by approximately 25%) and decreased the nonrenal clearances (by approximately 30%), indicating that T-3761 inhibits the metabolism of theophylline. These findings suggest that T-3761 at the dose used in this study affects the pharmacokinetics and metabolism of theophylline.

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Selected References

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  1. Edwards D. J., Waite N. M., Svensson C. K. Effect of enoxacin and 4-oxo-enoxacin on antipyrine disposition in the rat. Drug Metab Dispos. 1988 Jul-Aug;16(4):653–655. [PubMed] [Google Scholar]
  2. Fuhr U., Strobl G., Manaut F., Anders E. M., Sörgel F., Lopez-de-Brinas E., Chu D. T., Pernet A. G., Mahr G., Sanz F. Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isoform CYP1A2. Mol Pharmacol. 1993 Feb;43(2):191–199. [PubMed] [Google Scholar]
  3. Fuhr U., Wolff T., Harder S., Schymanski P., Staib A. H. Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes. Drug Metab Dispos. 1990 Nov-Dec;18(6):1005–1010. [PubMed] [Google Scholar]
  4. Fukuoka Y., Ikeda Y., Yamashiro Y., Takahata M., Todo Y., Narita H. In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative. Antimicrob Agents Chemother. 1993 Mar;37(3):384–392. doi: 10.1128/aac.37.3.384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gregoire S. L., Grasela T. H., Jr, Freer J. P., Tack K. J., Schentag J. J. Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects. Antimicrob Agents Chemother. 1987 Mar;31(3):375–378. doi: 10.1128/aac.31.3.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grygiel J. J., Birkett D. J. Cigarette smoking and theophylline clearance and metabolism. Clin Pharmacol Ther. 1981 Oct;30(4):491–496. doi: 10.1038/clpt.1981.193. [DOI] [PubMed] [Google Scholar]
  7. Grygiel J. J., Miners J. O., Drew R., Birkett D. J. Differential effects of cimetidine on theophylline metabolic pathways. Eur J Clin Pharmacol. 1984;26(3):335–340. doi: 10.1007/BF00548764. [DOI] [PubMed] [Google Scholar]
  8. Hasegawa T., Kuzuya T., Apichartpichean R., Nadai M., Nitta A., Takagi K., Nabeshima T. Structure-related inhibitory effect of quinolones on alkyl-xanthine elimination in rats. Pharmacol Toxicol. 1991 Jul;69(1):5–8. doi: 10.1111/j.1600-0773.1991.tb00399.x. [DOI] [PubMed] [Google Scholar]
  9. Hasegawa T., Nadai M., Kuzuya T., Muraoka I., Apichartpichean R., Takagi K., Miyamoto K. The possible mechanism of interaction between xanthines and quinolone. J Pharm Pharmacol. 1990 Nov;42(11):767–772. doi: 10.1111/j.2042-7158.1990.tb07018.x. [DOI] [PubMed] [Google Scholar]
  10. Hasegawa T., Yamaki K., Nadai M., Muraoka I., Wang L., Takagi K., Nabeshima T. Lack of effect of Chinese medicines on bioavailability of ofloxacin in healthy volunteers. Int J Clin Pharmacol Ther. 1994 Feb;32(2):57–61. [PubMed] [Google Scholar]
  11. Ho G., Tierney M. G., Dales R. E. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clin Pharmacol Ther. 1988 Jul;44(1):35–38. doi: 10.1038/clpt.1988.109. [DOI] [PubMed] [Google Scholar]
  12. Jenne J. W., Nagasawa H. T., Thompson R. D. Relationship of urinary metabolites of theophylline to serum theophylline levels. Clin Pharmacol Ther. 1976 Mar;19(3):375–381. doi: 10.1002/cpt1976193375. [DOI] [PubMed] [Google Scholar]
  13. Jonkman J. H., Upton R. A. Pharmacokinetic drug interactions with theophylline. Clin Pharmacokinet. 1984 Jul-Aug;9(4):309–334. doi: 10.2165/00003088-198409040-00002. [DOI] [PubMed] [Google Scholar]
  14. Kuzuya T., Takagi K., Apichartpichean R., Muraoka I., Nadai M., Hasegawa T. Kinetic interaction between theophylline and a newly developed quinolone, NY-198. J Pharmacobiodyn. 1989 Jul;12(7):405–409. doi: 10.1248/bpb1978.12.405. [DOI] [PubMed] [Google Scholar]
  15. Lohmann S. M., Miech R. P. Theophylline metabolism by the rat liver microsomal system. J Pharmacol Exp Ther. 1976 Jan;196(1):213–225. [PubMed] [Google Scholar]
  16. Nadai M., Hasegawa T., Kuzuya T., Muraoka I., Takagi K., Yoshizumi H. Effects of enoxacin on renal and metabolic clearance of theophylline in rats. Antimicrob Agents Chemother. 1990 Sep;34(9):1739–1743. doi: 10.1128/aac.34.9.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Raoof S., Wollschlager C., Khan F. A. Ciprofloxacin increases serum levels of theophylline. Am J Med. 1987 Apr 27;82(4A):115–118. [PubMed] [Google Scholar]
  18. Takagi K., Hasegawa T., Ogura Y., Suzuki R., Yamaki K., Watanabe T., Kitazawa S., Satake T. Comparative studies on interaction between theophylline and quinolones. J Asthma. 1988;25(2):63–71. doi: 10.3109/02770908809071356. [DOI] [PubMed] [Google Scholar]
  19. Takagi K., Yamaki K., Nadai M., Kuzuya T., Hasegawa T. Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients. Antimicrob Agents Chemother. 1991 Jun;35(6):1137–1141. doi: 10.1128/aac.35.6.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wijnands W. J., Vree T. B., van Herwaarden C. L. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol. 1986 Dec;22(6):677–683. doi: 10.1111/j.1365-2125.1986.tb02957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wijnands W. J., van Herwaarden C. L., Vree T. B. Enoxacin raises plasma theophylline concentrations. Lancet. 1984 Jul 14;2(8394):108–109. doi: 10.1016/s0140-6736(84)90283-6. [DOI] [PubMed] [Google Scholar]
  22. Williams J. F., Lowitt S., Szentivanyi A. Effects of phenobarbital and 3-methylcholanthrene pretreatment on the plasma half-life and urinary excretion profile of theophylline and its metabolites in rats. Biochem Pharmacol. 1979 Oct 1;28(19):2935–2940. doi: 10.1016/0006-2952(79)90589-6. [DOI] [PubMed] [Google Scholar]

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