Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1986 Feb;21(2):171–181. doi: 10.1111/j.1365-2125.1986.tb05172.x

Intra- and inter-individual variation in pharmacokinetics of intravenously infused amoxycillin and ampicillin to elderly volunteers.

J Sjövall, G Alván, B Huitfeldt
PMCID: PMC1400908  PMID: 3954933

Abstract

The purpose of this study was to investigate the disposition of two aminopenicillins and their intra- and inter-individual variation in pharmacokinetic parameters in healthy, elderly volunteers. Two groups, each of 12 active, community-dwelling volunteers between 69 and 83 years of age participated. One group was given 500 mg of amoxycillin, the other group 500 mg of ampicillin as single i.v. infusions. Within the drug groups each volunteer was given the infusion at two different occasions separated by a time-period of 1 week. Amoxycillin and ampicillin were determined in plasma and urine by modern column liquid chromatographic methods. The mean plasma clearance was about 200 ml min-1 1.73 m-2 for both drugs and renal clearance accounted for approximately 80% of this. As expected, drug clearance was correlated to renal function as determined by 51Cr-EDTA. The volume of distribution at steady-state (Vss) was about 0.3 l kg-1 for both drugs. Compared to our previous results in younger subjects, plasma and renal clearances were essentially similar in this study, but slightly longer half-lives and higher Vss were seen for amoxycillin and ampicillin. The intra-individual variation, expressed as the error of a single determination (CV), was small, for plasma clearance 3.7% and 6.4% after amoxycillin and ampicillin. The corresponding inter-individual variation in clearance was higher, 14.4% after amoxycillin, and 11.9% after ampicillin. The results confirm a higher relative efficiency of a crossover vs a completely randomized parallel groups design in parenteral studies of these penicillins. In our elderly subjects there was only an approximately 30% decrease in renal function. This was not enough to reduce the drug clearance and offers an explanation for the similarity between our present results in the elderly and our previous results in younger subjects. Elderly volunteers may be different from patients with disease as a confounding factor. Studies on elderly active and community-dwelling volunteers, as in this study, may therefore be more representative as to the effect of age per se on drug kinetics.

Full text

PDF
179

Selected References

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

  1. Carlqvist J., Westerlund D. Automated determination of amoxycillin in biological fluids by column switching in ion-pair reversed-phase liquid chromatographic systems with post-column derivatization. J Chromatogr. 1985 Nov 8;344:285–296. doi: 10.1016/s0378-4347(00)82029-0. [DOI] [PubMed] [Google Scholar]
  2. Chiou W. L. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J Pharmacokinet Biopharm. 1978 Dec;6(6):539–546. doi: 10.1007/BF01062108. [DOI] [PubMed] [Google Scholar]
  3. Cockcroft D. W., Gault M. H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. doi: 10.1159/000180580. [DOI] [PubMed] [Google Scholar]
  4. Crooks J., O'Malley K., Stevenson I. H. Pharmacokinetics in the elderly. Clin Pharmacokinet. 1976;1(4):280–296. doi: 10.2165/00003088-197601040-00003. [DOI] [PubMed] [Google Scholar]
  5. Landaw E. M., DiStefano J. J., 3rd Multiexponential, multicompartmental, and noncompartmental modeling. II. Data analysis and statistical considerations. Am J Physiol. 1984 May;246(5 Pt 2):R665–R677. doi: 10.1152/ajpregu.1984.246.5.R665. [DOI] [PubMed] [Google Scholar]
  6. Loo J. C., Riegelman S. Assessment of pharmacokinetic constants from postinfusion blood curves obtained after I.V. infusion. J Pharm Sci. 1970 Jan;59(1):53–55. doi: 10.1002/jps.2600590107. [DOI] [PubMed] [Google Scholar]
  7. Rowe J. W., Andres R., Tobin J. D., Norris A. H., Shock N. W. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol. 1976 Mar;31(2):155–163. doi: 10.1093/geronj/31.2.155. [DOI] [PubMed] [Google Scholar]
  8. Sedman A. J., Wagner J. G. CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci. 1976 Jul;65(7):1006–1010. doi: 10.1002/jps.2600650713. [DOI] [PubMed] [Google Scholar]
  9. Simon V. C., Malerczyk V., Zierott G., Lehmann K., Thiesen U. Blut-, Harn- und Gallespiegel von Ampicillin bei intravenöser Dauerinfusion. Arzneimittelforschung. 1975 Apr;25(4):654–656. [PubMed] [Google Scholar]
  10. Sjövall J., Alván G., Westerlund D. Dose-dependent absorption of amoxycillin and bacampicillin. Clin Pharmacol Ther. 1985 Sep;38(3):241–250. doi: 10.1038/clpt.1985.166. [DOI] [PubMed] [Google Scholar]
  11. Sjövall J., Westerlund D., Alván G. Renal excretion of intravenously infused amoxycillin and ampicillin. Br J Clin Pharmacol. 1985 Feb;19(2):191–201. doi: 10.1111/j.1365-2125.1985.tb02631.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Smith C., Ebrahim S., Arie T. Drug trials, the "elderly", and the very aged. Lancet. 1983 Nov 12;2(8359):1139–1139. doi: 10.1016/s0140-6736(83)90649-9. [DOI] [PubMed] [Google Scholar]
  13. Triggs E. J., Johnson J. M., Learoyd B. Absorption and disposition of ampicillin in the elderly. Eur J Clin Pharmacol. 1980 Aug;18(2):195–198. doi: 10.1007/BF00561590. [DOI] [PubMed] [Google Scholar]
  14. Tsuji A., Terasaki T., Imaeda N., Nishide K., Nakashima E. Effect of extracellular water volume on the distribution kinetics of beta-lactam antibiotics as a function of age. J Pharmacobiodyn. 1985 Mar;8(3):167–174. doi: 10.1248/bpb1978.8.167. [DOI] [PubMed] [Google Scholar]
  15. Westerlund D., Carlqvist J., Theodorsen A. Analysis of penicillins in biological material by reversed phase liquid chromatography and post-column derivatization. Acta Pharm Suec. 1979;16(3):187–214. [PubMed] [Google Scholar]
  16. Westlake W. J. Problems associated with analysis of pharmacokinetic models. J Pharm Sci. 1971 Jun;60(6):882–885. doi: 10.1002/jps.2600600616. [DOI] [PubMed] [Google Scholar]
  17. Yamaoka K., Nakagawa T., Uno T. Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm. 1978 Dec;6(6):547–558. doi: 10.1007/BF01062109. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES