Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1987 Mar;31(3):375–378. doi: 10.1128/aac.31.3.375

Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects.

S L Gregoire, T H Grasela Jr, J P Freer, K J Tack, J J Schentag
PMCID: PMC174735  PMID: 3472488

Abstract

The influence of multiple doses of ofloxacin (ORF 18489) on the disposition of theophylline was studied in 15 male volunteers. Subjects were confined in the Clinical Research Unit for 13 days and given a xanthine-free diet. A single dose (3 mg/kg) of theophylline was given orally, and blood samples were collected at fixed time intervals for 36 h. The concentrations of theophylline were measured with TDX (Abbott Diagnostics, Irving, Tex.), and clearance was calculated. Theophylline clearance was used to individualize subsequent doses to achieve average steady-state theophylline concentrations in plasma of 10 mg/liter. Individualized theophylline doses were administered every 8 h until steady-state conditions were reached. Theophylline clearance was determined again at steady state and on days 7 and 8. On day 8, ofloxacin (400 mg every 12 h) was given concomitantly with theophylline. Theophylline clearance was measured again on day 12, after the last theophylline dose. Administration of ofloxacin for 1 day did not change theophylline clearance, but coadministration for 4 days significantly decreased theophylline clearance by 12.1% (P less than 0.05). The area under the concentration-time curve for theophylline increased 9.9% (P less than 0.05), and average steady-state concentrations in plasma increased 10.3% (P less than 0.05). Despite changes in clearance, adverse effects of theophylline did not increase during coadministration of ofloxacin. Although statistically significant, the interaction between ofloxacin and theophylline is unlikely to be of major clinical importance.

Full text

PDF
375

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Fourtillan J. B., Granier J., Saint-Salvi B., Salmon J., Surjus A., Tremblay D., Vincent Du Laurier M., Beck S. Pharmacokinetics of ofloxacin and theophylline alone and in combination. Infection. 1986;14 (Suppl 1):S67–S69. doi: 10.1007/BF01645203. [DOI] [PubMed] [Google Scholar]
  2. Fraser A. G., Harrower A. D. Convulsions and hyperglycaemia associated with nalidixic acid. Br Med J. 1977 Dec 10;2(6101):1518–1518. doi: 10.1136/bmj.2.6101.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Galland M. C., Jouve-Bestagne M. H., Rodor F., Jouglard J. Effets indésirables neurologiques des quinolones antibactériens urinaires. Therapie. 1982 Jul-Aug;37(4):481–487. [PubMed] [Google Scholar]
  4. Hendeles L., Weinberger M. Theophylline. A "state of the art" review. Pharmacotherapy. 1983 Jan-Feb;3(1):2–44. doi: 10.1002/j.1875-9114.1983.tb04531.x. [DOI] [PubMed] [Google Scholar]
  5. Jusko W. J., Gardner M. J., Mangione A., Schentag J. J., Koup J. R., Vance J. W. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. J Pharm Sci. 1979 Nov;68(11):1358–1366. doi: 10.1002/jps.2600681106. [DOI] [PubMed] [Google Scholar]
  6. Lockley M. R., Wise R., Dent J. The pharmacokinetics and tissue penetration of ofloxacin. J Antimicrob Chemother. 1984 Dec;14(6):647–652. doi: 10.1093/jac/14.6.647. [DOI] [PubMed] [Google Scholar]
  7. Powell-Jackson P. R., Jamieson A. P., Gray B. J., Moxham J., Williams R. Effect of rifampicin administration on theophylline pharmacokinetics in humans. Am Rev Respir Dis. 1985 Jun;131(6):939–940. doi: 10.1164/arrd.1985.131.6.939. [DOI] [PubMed] [Google Scholar]
  8. Reitberg D. P., Bernhard H., Schentag J. J. Alteration of theophylline clearance and half-life by cimetidine in normal volunteers. Ann Intern Med. 1981 Nov;95(5):582–585. doi: 10.7326/0003-4819-95-5-582. [DOI] [PubMed] [Google Scholar]
  9. Saito A., Sawatari K., Fukuda Y., Nagasawa M., Koga H., Tomonaga A., Nakazato H., Fujita K., Shigeno Y., Suzuyama Y. Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs. Antimicrob Agents Chemother. 1985 Jul;28(1):15–20. doi: 10.1128/aac.28.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sato K., Matsuura Y., Inoue M., Une T., Osada Y., Ogawa H., Mitsuhashi S. In vitro and in vivo activity of DL-8280, a new oxazine derivative. Antimicrob Agents Chemother. 1982 Oct;22(4):548–553. doi: 10.1128/aac.22.4.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Tsukamura M. In vitro antituberculosis activity of a new antibacterial substance ofloxacin (DL8280). Am Rev Respir Dis. 1985 Mar;131(3):348–351. doi: 10.1164/arrd.1985.131.3.348. [DOI] [PubMed] [Google Scholar]
  12. Tsukamura M., Nakamura E., Yoshii S., Amano H. Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis. Am Rev Respir Dis. 1985 Mar;131(3):352–356. doi: 10.1164/arrd.1985.131.3.352. [DOI] [PubMed] [Google Scholar]
  13. 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]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES