Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1977 Jan;11(1):132–141. doi: 10.1128/aac.11.1.132

Pharmacokinetics of Amoxicillin: Dose Dependence After Intravenous, Oral, and Intramuscular Administration

Daniel A Spyker *, Raymond J Rugloski 1, Robert L Vann 1, William M O'Brien 1
PMCID: PMC351932  PMID: 836010

Abstract

Amoxicillin was studied in normal subjects after intravenous, oral, and intramuscular administration of 250-, 500-, and 1,000-mg doses. Serum drug levels were analyzed using a two-compartment open model, as well as area under the curve (AUC) and urinary recovery. The variations of these pharmacokinetic parameters were then examined using the three-way analysis of variance and linear regression equations. These results confirmed nearly complete oral absorption: AUC was 93% of intravenous absorption, and urinary recovery was 86%. The intramuscular administration of amoxicillin results in complete and reliable absorption with peak drug levels, AUCs, and urinary recovery equivalent to oral dosage. The absorption of lyophilized amoxicillin after intramuscular injection resulted in an AUC that was 92% of intravenous absorption and urinary recovery of 91%. The peak serum levels, time to peak, and other pharmacokinetic parameters for intramuscular injection were nearly identical to those for oral administration. Kinetics of both intramuscular and oral administration exhibited dose-dependent absorption (absorption rate constant, 1.3/h for 250 mg and 0.7/h for 1,000 mg). This resulted in relatively later and lower peak serum levels for increasing dose. Total absorption, however, showed no dose dependence, as indicated by urinary recovery and AUC, which changed by less than 10%.

Full text

PDF
132

Selected References

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

  1. Baird E. S., Hailey D. M. Plasma levels of diazepam and its major metabolite following intramuscular administration. Br J Anaesth. 1973 Jun;45(6):546–548. doi: 10.1093/bja/45.6.546. [DOI] [PubMed] [Google Scholar]
  2. Bennett J. V., Brodie J. L., Benner E. J., Kirby W. M. Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol. 1966 Mar;14(2):170–177. doi: 10.1128/am.14.2.170-177.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bischoff K. B., Dedrick R. L. Generalized solution to linear, to-compartment, open model for drug distribution. J Theor Biol. 1970 Oct;29(1):63–68. doi: 10.1016/0022-5193(70)90119-0. [DOI] [PubMed] [Google Scholar]
  4. Bodey G. P., Nance J. Amoxicillin: in vitro and pharmacological studies. Antimicrob Agents Chemother. 1972 Apr;1(4):358–362. doi: 10.1128/aac.1.4.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gordon C., Regamey C., Kirby W. M. Comparative clinical pharmacology of amoxicillin and ampicillin administered orally. Antimicrob Agents Chemother. 1972 Jun;1(6):504–507. doi: 10.1128/aac.1.6.504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Greenblatt D. J., Koch-Weser J. Clinical pharmacokinetics (second of two parts). N Engl J Med. 1975 Nov 6;293(19):964–970. doi: 10.1056/NEJM197511062931905. [DOI] [PubMed] [Google Scholar]
  7. Greenblatt D. J., Kock-Weser J. Drug therapy. Clinical Pharmacokinetics (first of two parts). N Engl J Med. 1975 Oct 2;293(14):702–705. doi: 10.1056/NEJM197510022931406. [DOI] [PubMed] [Google Scholar]
  8. Greenblatt D. J., Shader R. I. Drug therapy. Benzodiazepines (first of two parts). N Engl J Med. 1974 Nov 7;291(19):1011–1015. doi: 10.1056/NEJM197411072911906. [DOI] [PubMed] [Google Scholar]
  9. Handsfield H. H., Clark H., Wallace J. F., Holmes K. K., Turck M. Amoxicillin, a new penicillin antibiotic. Antimicrob Agents Chemother. 1973 Feb;3(2):262–265. doi: 10.1128/aac.3.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harding J. W., Lees L. J. Trial of a new broad-spectrum penicillin (amoxycillin) in general practice. Practitioner. 1972 Sep;209(251):363–368. [PubMed] [Google Scholar]
  11. Leigh D. A. Diagnosis of urinary tract infections in general practice, and treatment with a new penicillin--amoxycillin. Curr Med Res Opin. 1972;1(1):10–18. doi: 10.1185/03007997209111140. [DOI] [PubMed] [Google Scholar]
  12. Middleton F. G., Poretz D. M., Duma R. J. Clinical and laboratory evaluation of amoxicillin (BRL 2333) in the treatment of urinary tract infections. Antimicrob Agents Chemother. 1973 Jul;4(1):25–30. doi: 10.1128/aac.4.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Neu H. C., Winshell E. B. Pharmacological studies of 6 (D(-) -amino-p-hydroxyphenylacetamido) penicillanic acid in humans. Antimicrob Agents Chemother (Bethesda) 1970;10:423–426. [PubMed] [Google Scholar]
  14. Philipson A., Sabath L. D., Rosner B. Sequence effect on ampicillin blood levels noted in an amoxicillin, ampicillin, and epicillin triple crossover study. Antimicrob Agents Chemother. 1975 Sep;8(3):311–320. doi: 10.1128/aac.8.3.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Riegelman S., Loo J. C., Rowland M. Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J Pharm Sci. 1968 Jan;57(1):117–123. doi: 10.1002/jps.2600570123. [DOI] [PubMed] [Google Scholar]
  16. Serrano E. E., Roye D. B., Hammer R. H., Wilder B. J. Plasma diphenylhydantoin values after oral and intramuscular administration of diphenylhydantoin. Neurology. 1973 Mar;23(3):311–317. doi: 10.1212/wnl.23.3.311. [DOI] [PubMed] [Google Scholar]
  17. Stam J. Preliminary clinical study with amoxycillin (BRL 2333) in complicated lower respiratory tract infections. Chemotherapy. 1973;18(Suppl):27–33. doi: 10.1159/000221291. [DOI] [PubMed] [Google Scholar]
  18. Sutherland R., Croydon E. A., Rolinson G. N. Amoxycillin: a new semi-synthetic penicillin. Br Med J. 1972 Jul 1;3(5817):13–16. doi: 10.1136/bmj.3.5817.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. WAGNER J. G., NELSON E. KINETIC ANALYSIS OF BLOOD LEVELS AND URINARY EXCRETION IN THE ABSORPTIVE PHASE AFTER SINGLE DOSES OF DRUG. J Pharm Sci. 1964 Nov;53:1392–1403. doi: 10.1002/jps.2600531126. [DOI] [PubMed] [Google Scholar]
  20. WAGNER J. G., NELSON E. Per cent absorbed time plots derived from blood level and/or urinary excretion data. J Pharm Sci. 1963 Jun;52:610–611. doi: 10.1002/jps.2600520629. [DOI] [PubMed] [Google Scholar]
  21. Wilensky A. J., Lowden J. A. Inadequate serum levels after intramuscular administration of diphenylhydantoin. Neurology. 1973 Mar;23(3):318–324. doi: 10.1212/wnl.23.3.318. [DOI] [PubMed] [Google Scholar]
  22. Zarowny D., Ogilvie R., Tamblyn D., MacLeod C., Ruedy J. Pharmacokinetics of amoxicillin. Clin Pharmacol Ther. 1974 Dec;16(6):1045–1051. doi: 10.1002/cpt19741661045. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES