title: [Effect of antiinflammatory agents on the accumulation of ofloxacin in human polymorphonuclear leukocytes].
abstract: The uptake of quinolones is a recently defined pharmacokinetic parameter which is increasing in importance in clinical practice, especially for immunocompromised patients whose polymorphonuclear leukocytes (PMNLs) have their bactericidal systems impaired, or in infections due to bacteria able to survive in the phagocytes. In both situations, antibiotics able to penetrate and be active in the phagocytes are required. The simultaneous administration of an antibiotic and an antiinflammatory drug is frequent, and previous studies have described interactions between the intracellular activity of the quinolones and the presence of phenylbutazone. We studied the effect of the presence of and the pretreatment (37 C for 30 and 60 min) of human PMNLs with the antiinflammatory drugs betamethasone (1 mg/l), hydrocortisone (1 mg/l), phenylbutazone (10 mg/ml), and acetylsalicylic acid (200 mg/l) on the uptake of ofloxacin (10 mg/l) by the PMNLs using a fluorometric method to measure the intra-PMNL concentration of ofloxacin. The presence of betamethasone did not modify the uptake of ofloxacin by PMNLs. Pretreatment of PMNLs with hydrocortisone, phenylbutazone and acetylsalicylic acid produced a significant decrease in the maximum intracellular concentration/extracellular concentration ratios compared with the maximum reached without pretreatment. These results suggest that hydrocortisone, phenylbutazone and acetylsalicylic acid interfere with the uptake of ofloxacin by PMNLs and increase the efflux of ofloxacin from PMNLs.
authors.affiliation: Unidad de Bacteriología Experimental del Centro de Investigación, Hospital Universitario La Fe, Valencia.
authors.forename: A
authors.initials: A
authors.lastname: Orero
authors.forename: E
authors.initials: E
authors.lastname: Cantón
authors.forename: M V
authors.initials: MV
authors.lastname: Bermejo
authors.forename: M M
authors.initials: MM
authors.lastname: Velert
authors.forename: E
authors.initials: E
authors.lastname: Cabrera
authors.forename: J
authors.initials: J
authors.lastname: Pemán
authors.forename: M
authors.initials: M
authors.lastname: Gobernado
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D015242:Ofloxacin / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D015242:Ofloxacin