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Influence of brodimoprim on polymorphonuclear leukocyte phagocytosis and oxidant radical production
P C Braga1, M Dal Sasso, S Maci
1Department of Pharmacology, University of Milan, Italy.
Abstract:
Antibiotics not only reach the site of infection, but also penetrate cyclically, during a treatment, into polymorphonuclear leukocytes (PMNs) and may influence their functions positively or negatively. With reference to these aspects, the influence of brodimoprim (BMP), a dimethoxybenzylpyrimidine recently entered into clinical use, on human PMN phagocytosis and oxidant radical production (chemiluminescence) was investigated. PMNs from healthy adult donors were incubated for 50 min in medium alone or in medium containing increasing concentrations (3.7, 7.5, 15, and 30 micrograms/ml) of BMP and trimethoprim (TMP). In unwashed PMNs, phagocytosis was not modified by BMP, but was significantly reduced by 30 micrograms/ml TMP; chemiluminescence was significantly reduced by 15 and 30 micrograms/ml BMP and by all concentrations of TMP. When PMNs were washed after incubation, phagocytosis was unaffected and chemiluminescence was significantly restored. BMP at therapeutic concentrations did not influence PMNs and was less toxic than TMP.
Insights
Brodimoprim (BMP) did not affect human polymorphonuclear leukocyte (PMN) functions at therapeutic doses. Unlike trimethoprim (TMP), BMP showed less toxicity to PMNs.
Area of Science:
- Pharmacology
- Immunology
- Antimicrobial Agents
Background:
- Antibiotics can penetrate polymorphonuclear leukocytes (PMNs), potentially altering their function.
- Understanding these interactions is crucial for optimizing antibiotic therapy.
- Brodimoprim (BMP) is a new dimethoxybenzylpyrimidine antibiotic.
Purpose of the Study:
- To investigate the effects of brodimoprim (BMP) on human PMN phagocytosis and oxidant radical production.
- To compare the effects of BMP with trimethoprim (TMP) on PMN function.
- To assess the toxicity of BMP and TMP on PMNs.
Main Methods:
- Human PMNs were incubated with varying concentrations of BMP and TMP.
- Phagocytosis and chemiluminescence (oxidant radical production) were measured.
- Experiments were conducted with both unwashed and washed PMNs to evaluate drug reversibility.
Main Results:
- BMP did not significantly alter PMN phagocytosis.
- TMP significantly reduced phagocytosis at 30 micrograms/ml in unwashed PMNs.
- BMP reduced chemiluminescence at 15 and 30 micrograms/ml, while TMP reduced it at all tested concentrations.
- Washing PMNs restored chemiluminescence, indicating reversible effects.
- BMP demonstrated lower toxicity compared to TMP at therapeutic concentrations.
Conclusions:
- Brodimoprim (BMP) at therapeutic concentrations does not impair human PMN phagocytosis or oxidant radical production.
- BMP exhibits less toxicity to PMNs than trimethoprim (TMP).
- The observed effects of BMP on PMN function are reversible upon removal of the drug.