THE PENETRATION OF COTRIMOXAZOLE INTO ALVEOLAR MACROPHAGES AND ITS EFFECT ON INFLAMMATORY AND IMMUNOREGULATORY FUNCTIONS

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 trimethopnm (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·±0·) 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. © 1990, by The British Society for Antimicrobial Chemotherapy.