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Benzylpenicillin in mice. Effect of meningococci on plasma concentrations
Abstract:
Plasma concentration studies were performed in mice given high intravenous (i.v.) bolus injections or subcutaneous (s.c.) depot doses of benzylpenicillin. There was a marked difference in plasma concentration within and between individuals both after benzylpenicillin (BP) given i.v. and after benzylpenicillin procaine (BPP) given s.c. BP given i.v. resulted in a plasma half-life of 15.2 minutes, while BPP given s.c. resulted in a plasma half-life of 2.7 hours. Infection with an endotoxin-liberating meningococcal strain in BP-treated animals increased the plasma levels of BP compared with uninfected controls.
Insights
Benzylpenicillin (BP) administered intravenously and Benzylpenicillin Procaine (BPP) administered subcutaneously showed significant differences in plasma concentration and half-life in mice. Infection increased BP plasma levels.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Microbiology and Infectious Diseases
Background:
- Understanding the pharmacokinetic profiles of antibiotics like benzylpenicillin is crucial for effective treatment strategies.
- Variability in drug absorption and elimination can significantly impact therapeutic outcomes, especially in infectious disease contexts.
Purpose of the Study:
- To investigate and compare the plasma concentration and half-life of benzylpenicillin (BP) administered via intravenous (i.v.) bolus versus subcutaneous (s.c.) depot injection of Benzylpenicillin Procaine (BPP) in mice.
- To assess the impact of endotoxin-liberating meningococcal infection on the plasma levels of benzylpenicillin.
Main Methods:
- Plasma concentration studies were conducted in mice following high-dose i.v. bolus injections of BP.
- Plasma concentration studies were performed in mice following s.c. depot doses of BPP.
- Mice infected with an endotoxin-liberating meningococcal strain were used to evaluate the effect of infection on BP plasma levels compared to uninfected controls.
Main Results:
- A marked inter-individual and intra-individual variability in plasma concentrations was observed for both i.v. BP and s.c. BPP.
- Benzylpenicillin (BP) administered i.v. exhibited a short plasma half-life of 15.2 minutes.
- Benzylpenicillin Procaine (BPP) administered s.c. demonstrated a significantly longer plasma half-life of 2.7 hours.
- Infection with the meningococcal strain led to increased plasma levels of BP in treated animals compared to uninfected controls.
Conclusions:
- Subcutaneous depot administration of Benzylpenicillin Procaine results in a prolonged plasma half-life compared to intravenous administration of Benzylpenicillin.
- Infection can influence the pharmacokinetics of benzylpenicillin, potentially affecting drug efficacy.
- The findings highlight the importance of formulation and route of administration in determining benzylpenicillin's pharmacokinetic behavior and suggest infection-mediated alterations.