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High teicoplanin uptake by human neutrophils
E G Maderazo1, S P Breaux, C L Woronick
1Department of Medicine, Hartford Hospital, Conn.
Chemotherapy
|January 1, 1988
Summary
Teicoplanin accumulates rapidly in polymorphonuclear leukocytes (PMNs) via an active process, retaining antimicrobial activity. However, teicoplanin inhibits PMN functions at high and low concentrations, respectively.
Area of Science:
- Pharmacokinetics and cellular pharmacology
- Immunology and infectious diseases
Background:
- Teicoplanin is an important antibiotic used to treat Gram-positive bacterial infections.
- Understanding its interaction with immune cells like polymorphonuclear leukocytes (PMNs) is crucial for assessing its efficacy and potential side effects.
Purpose of the Study:
- To investigate the cellular uptake, intracellular concentration, and functional effects of teicoplanin in PMNs.
- To determine the time- and concentration-dependency of teicoplanin accumulation in PMNs.
Main Methods:
- Measurement of teicoplanin cellular/extracellular (C/E) concentration ratios in PMNs over time.
- Assessment of teicoplanin's effect on PMN chemotaxis and microbicidal activity.
- Evaluation of drug retention after washing PMNs.
Main Results:
- The C/E ratio of teicoplanin in PMNs increased rapidly and was time- and concentration-dependent.
- Cellular drug concentration reached 4,700 +/- 1,300 micrograms/ml at 20 minutes with an initial concentration of 75 +/- 16 micrograms/ml.
- Teicoplanin uptake is an active process, and the intracellular drug retained antimicrobial activity.
- Washing removed 42% of cellular teicoplanin.
- Teicoplanin inhibited PMN chemotaxis at high concentrations and microbicidal activity at lower concentrations.
Conclusions:
- Teicoplanin actively accumulates in PMNs, maintaining its antimicrobial properties.
- The drug's interaction with PMNs can modulate immune cell function, potentially impacting therapeutic outcomes and side effect profiles.