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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1985 May;19(5):657–668. doi: 10.1111/j.1365-2125.1985.tb02693.x

Comparative pharmacodynamics and clinical pharmacokinetics of phenoxymethylpenicillin and pheneticillin.

D Overbosch, H Mattie, R van Furth
PMCID: PMC1463849  PMID: 3924086

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BARBER M., WATERWORTH P. M. Antibacterial activity of the penicillins. Br Med J. 1962 Apr 28;1(5286):1159–1164. doi: 10.1136/bmj.1.5286.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BERLIN H., BRANTE G. Studies on oral utilization of penicillin V. Antibiot Annu. 1958;6:149–157. [PubMed] [Google Scholar]
  3. BOND J. M., BARBER M., LIGHTBOWN J. W., WATERWORTH P. M. A COMPARISON OF FOUR PHENOXYPENICILLINS. Br Med J. 1963 Oct 19;2(5363):956–961. doi: 10.1136/bmj.2.5363.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bergan T., Berdal B. P., Holm V. Relative bioavailability of phenoxymethylpenicillin preparations in a cross-over study. Acta Pharmacol Toxicol (Copenh) 1976 Apr;38(4):308–320. doi: 10.1111/j.1600-0773.1976.tb03125.x. [DOI] [PubMed] [Google Scholar]
  5. Biagi G. L., Guerra M. C., Barbaro A. M., Gamba M. F. Influence of lipophilic character on the antibacterial activity of cephalosporins and penicillins. J Med Chem. 1970 May;13(3):511–516. doi: 10.1021/jm00297a038. [DOI] [PubMed] [Google Scholar]
  6. Bolme P., Eriksson M. Influence of diarrhea on the oral absorption of penicillin V and ampicillin in children. Scand J Infect Dis. 1975;7(2):141–145. doi: 10.3109/inf.1975.7.issue-2.11. [DOI] [PubMed] [Google Scholar]
  7. GARROD L. P. The relative antibacterial activity of four penicillins. Br Med J. 1960 Dec 10;2(5214):1695–1696. doi: 10.1136/bmj.2.5214.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. George C. F. Diseases of the alimentary system. Absorption, distribution, and metabolism of drugs; effects of disease of the gut. Br Med J. 1976 Sep 25;2(6038):742–744. doi: 10.1136/bmj.2.6038.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KRAUSHAAR A., GIOVANNINI M. Comparative investigations with acid penicillin V and a water-soluble penicillin V salt under different conditions. Antibiot Annu. 1958;6:158–163. [PubMed] [Google Scholar]
  10. Kates R. E., Harapat S. R., Keefe D. L., Goldwater D., Harrison D. C. Influence of prolonged recumbency on drug disposition. Clin Pharmacol Ther. 1980 Nov;28(5):624–628. doi: 10.1038/clpt.1980.213. [DOI] [PubMed] [Google Scholar]
  11. Klotz U. Pathophysiological and disease-induced changes in drug distribution volume: pharmacokinetic implications. Clin Pharmacokinet. 1976;1(3):204–218. doi: 10.2165/00003088-197601030-00003. [DOI] [PubMed] [Google Scholar]
  12. Kunin C. M. Clinical pharmacology of the new penicillins. 1. The importance of serum protein binding in determining antimicrobial activity and concentration in serum. Clin Pharmacol Ther. 1966 Mar-Apr;7(2):166–179. doi: 10.1002/cpt196672166. [DOI] [PubMed] [Google Scholar]
  13. Kunst M. W., Mattie H. Absorption of pivampicillin in postoperative patients. Antimicrob Agents Chemother. 1975 Jul;8(1):11–14. doi: 10.1128/aac.8.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kunst M. W., Mattie H. Cefazolin and cephradine: relationship between antibacterial activity in vitro and in mice experimentally infected with Escherichia coli. J Infect Dis. 1978 Apr;137(4):391–402. doi: 10.1093/infdis/137.4.391. [DOI] [PubMed] [Google Scholar]
  15. Loo J. C., Riegelman S. New method for calculating the intrinsic absorption rate of drugs. J Pharm Sci. 1968 Jun;57(6):918–928. doi: 10.1002/jps.2600570602. [DOI] [PubMed] [Google Scholar]
  16. Mattie H., Goslings W. R., Noach E. L. Cloxacillin and nafcillin: serum binding and its relationship to antibacterial effect in mice. J Infect Dis. 1973 Aug;128(2):170–177. doi: 10.1093/infdis/128.2.170. [DOI] [PubMed] [Google Scholar]
  17. Mattie H., van der Voet G. B. The relative potency of amoxycillin and ampicillin in vitro and in vivo. Scand J Infect Dis. 1981;13(4):291–296. doi: 10.3109/inf.1981.13.issue-4.10. [DOI] [PubMed] [Google Scholar]
  18. Mawer G. E., Lucas S. B., Knowles B. R., Stirland R. M. Computer-assisted prescribing of kanamycin for patients with renal insufficiency. Lancet. 1972 Jan 1;1(7740):12–15. doi: 10.1016/s0140-6736(72)90005-0. [DOI] [PubMed] [Google Scholar]
  19. Nimmo W. S. Drugs, diseases and altered gastric emptying. Clin Pharmacokinet. 1976;1(3):189–203. doi: 10.2165/00003088-197601030-00002. [DOI] [PubMed] [Google Scholar]
  20. PECK F. B., Jr, GRIFFITH R. S. Comparative clinical laboratory studies of potassium penicillin V with acid penicillin V. Antibiot Annu. 1957;5:1004–1013. [PubMed] [Google Scholar]
  21. Palatsi I., Kaipainen W. A comparative study of blood concentrations after peroral benzathine (DBED) penicillin V and potassium penicillin V. Scand J Infect Dis. 1971;3(1):71–74. doi: 10.3109/inf.1971.3.issue-1.13. [DOI] [PubMed] [Google Scholar]
  22. SPITZY K. H., DOUJAK P. H. Blood levels after oral administration of penicillin V acid or penicillin V salt in relation to gastric acidity. Antibiot Annu. 1958;6:165–167. [PubMed] [Google Scholar]
  23. Sabath L. D. Phenoxymethylpenicillin (penicillin V) and phenethicillin. Med Clin North Am. 1970 Sep;54(5):1101–1111. [PubMed] [Google Scholar]
  24. Siersbaek-Nielsen K., Hansen J. M., Kampmann J., Kristensen M. Rapid evaluation of creatinine clearance. Lancet. 1971 May 29;1(7709):1133–1134. doi: 10.1016/s0140-6736(71)91873-3. [DOI] [PubMed] [Google Scholar]
  25. Simon C., Malerczyk V., Wulffen CGv In-vitro-Aktivitat und Pharmakokinetik von Propicillin, Penicillin V und Phenethicillin. Med Welt. 1976 Dec 17;27(51):2476–2481. [PubMed] [Google Scholar]
  26. Welling P. G., Tse F. L. The influence of food on the absorption of antimicrobial agents. J Antimicrob Chemother. 1982 Jan;9(1):7–27. doi: 10.1093/jac/9.1.7. [DOI] [PubMed] [Google Scholar]
  27. Yasuhara H., Kobayashi S., Sakamoto K., Kamijo K. Pharmacokinetics of amikacin and cephalothin in bedridden elderly patients. J Clin Pharmacol. 1982 Aug-Sep;22(8-9):403–409. doi: 10.1002/j.1552-4604.1982.tb02693.x. [DOI] [PubMed] [Google Scholar]
  28. van der Voet G. B., Mattie H., van Furth R. Quantitative determination of the effect of granulocytes on the course of experimental infections during antibiotic treatment. Infection. 1984 Jan-Feb;12(1):5–9. doi: 10.1007/BF01641015. [DOI] [PubMed] [Google Scholar]

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