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Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

Abstract
In this study the antimicrobial effects of phenoxymethylpenicillin (PM) and pheneticillin (PE) in vitro and in an experimental animal infection model were compared as well as the pharmacokinetic properties of both drugs in patients. For the inhibitory effect of PM on short-term (3 h) growth of S. aureus in vitro, this drug was 2.13 times more potent than PE. The protein binding of both drugs was similar (78-80%). The potency ratio of PM to PE against S. aureus in an experimental mouse-thigh infection was only 1.25 to 1. This is explained by the difference in the AUC after subcutaneous administration of PM (0.47 mg 1(-1) h) and PE (0.92 mg 1(-1) h). The plasma clearance after intravenous administration of PM was 476.4 ml/min and that of PE was 295.1 ml/min; the plasma clearance of both drugs was strongly correlated with the creatinine clearance. The volume of distribution in the steady state of PM was 35.41 and that of PE 22.51. In 10 patients, the absorption after oral administration of PM as the acid was 48% and that of the potassium salt of PE was 86% of the dose. From the present results it can be concluded that a difference in effectiveness of different formulations of PM and PE would depend entirely on differences in absorption.
AuthorsD Overbosch, H Mattie, R van Furth
JournalBritish journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 19 Issue 5 Pg. 657-68 (May 1985) ISSN: 0306-5251 [Print] ENGLAND
PMID3924086 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Proteins
  • Creatinine
  • phenethicillin
  • Penicillin V
Topics
  • Adult
  • Aged
  • Animals
  • Bacterial Infections (drug therapy)
  • Blood Bactericidal Activity
  • Blood Proteins (metabolism)
  • Creatinine (blood)
  • Female
  • Humans
  • Intestinal Absorption
  • Kinetics
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Middle Aged
  • Penicillin V (analogs & derivatives, blood, pharmacology, therapeutic use)
  • Protein Binding
  • Staphylococcal Infections (drug therapy)
  • Staphylococcus aureus (drug effects, growth & development)
  • Tissue Distribution

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