title: The penetration of co-trimoxazole into alveolar macrophages and its effect on inflammatory and immunoregulatory functions.
abstract: The pharmacokinetics of co-trimoxazole in serum, bronchoalveolar lavage-fluid (BAL-fluid) and alveolar macrophages (AM) of guinea pigs receiving sulphamethoxazole (100 mg/kg) and trimethoprim (20 mg/kg) were studied. HPLC showed that peak co-trimoxazole levels were obtained in serum at 30 min, in BAL-fluid at 1 h and in AM at 3 h. A comparison between mean concentrations in serum, BAL-fluid and AM showed a six-fold higher concentration of trimethoprim in cells than in serum, but only 0.25-fold of sulphamethoxazole. The BAL-fluid/serum ratio was four to ten times higher for trimethoprim than for sulphamethoxazole (0.6-to-one-fold). Sulphamethoxazole/trimethoprim ratios (30 min, 1 and 3 h) were lower in BAL-fluid (4.9 +/- 0.5) and in AM (1.4 +/- 0.5) than in serum (30.7 +/- 1.6). The influence of co-trimoxazole in vitro on microbicidal capacities (superoxide anion and hydrogen peroxide generations), immunoregulation (production of interleukin 1) and pro-inflammatory agent production (tumour necrosis factor) of guinea pigs' AM was also studied. No significant effect of co-trimoxazole on superoxide anion and hydrogen peroxide generations, or on interleukin 1 and TNF production, was demonstrable.
authors.affiliation: Laboratoire de Pathologie Respiratoire Expérimentale et de Pollution Atmosphérique, Institut Pasteur, Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Dubar
authors.forename: I
authors.initials: I
authors.lastname: Lopez
authors.forename: P
authors.initials: P
authors.lastname: Gosset
authors.forename: C
authors.initials: C
authors.lastname: Aerts
authors.forename: C
authors.initials: C
authors.lastname: Voisin
authors.forename: B
authors.initials: B
authors.lastname: Wallaert
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism; D007109:Immunity / Q000187:drug effects*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000493:pharmacokinetics* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D006861:Hydrogen Peroxide