Antibiotic penetration into normal and inflamed tissues as reflected by peripheral lymph
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Abstract:
The concentration of antibiotic in peripheral lymph reflects the tissue levels. Following microsurgical cannulation of the right lymphatic duct in 28 healthy rabbits, either penicillin-G, nafcillin, erythromycin, or cefazolin was given intramuscularly, and lymph and serum samples obtained at frequent intervals. Penicillin or nafcillin was administered to 14 additional rabbits with cellulitis of the right upper extremity. A serum sample drawn between one and two hours after an intramuscular injection, in general, reflects the peak lymph antibiotic concentration and hence the peak tissue concentration of the drug. After two hours the lymph level remains equal to or greater than the simultaneous serum level. The presence of inflammation did not alter the peak antibiotic levels. However, nafcillin required longer for equilibration in the inflamed state than in the uninflamed state, whereas penicillin-G equilibrated more rapidly in the presence of inflammation.
Insights
Serum antibiotic levels between one and two hours after injection reflect peak tissue concentrations. Lymph antibiotic levels remain equal to or greater than serum levels after two hours, indicating effective tissue penetration.
Area of Science:
- Pharmacology
- Microbiology
- Surgical Research
Background:
- Antibiotic concentration in peripheral lymph correlates with tissue drug levels.
- Understanding antibiotic pharmacokinetics in tissues is crucial for effective treatment.
- Lymphatic system plays a role in drug distribution.
Purpose of the Study:
- To determine the relationship between serum and lymph antibiotic concentrations.
- To assess the impact of inflammation on antibiotic distribution in tissues.
- To evaluate the pharmacokinetic profiles of penicillin-G, nafcillin, erythromycin, and cefazolin in lymph and serum.
Main Methods:
- Microsurgical cannulation of the right lymphatic duct in 28 healthy rabbits.
- Intramuscular administration of penicillin-G, nafcillin, erythromycin, or cefazolin.
- Serial collection of lymph and serum samples for antibiotic concentration analysis.
- Administration of penicillin-G or nafcillin to rabbits with induced cellulitis to study inflamed states.
Main Results:
- Serum antibiotic levels 1-2 hours post-injection generally reflect peak lymph (tissue) concentrations.
- After 2 hours, lymph antibiotic levels were consistently equal to or greater than serum levels.
- Inflammation did not significantly alter peak antibiotic levels.
- Nafcillin showed slower equilibration in inflamed tissue compared to uninflamed tissue.
- Penicillin-G demonstrated faster equilibration in inflamed tissue.
Conclusions:
- Serum antibiotic levels can serve as a surrogate for peak tissue concentrations within 1-2 hours of intramuscular administration.
- Antibiotics maintain therapeutic concentrations in lymphatic tissue beyond 2 hours post-injection.
- The presence of inflammation can differentially affect the pharmacokinetic equilibration of certain antibiotics, such as nafcillin and penicillin-G.