Enviromental Influences on Gentamicin Pharmacokinetics by Using Population Pharmacokinetic Methods

모집단 약물동태학 방법에 의한 겐타마이신 약물동태에 미치는 환경의 영향

  • Received : 2012.01.03
  • Accepted : 2012.02.01
  • Published : 2012.02.29

Abstract

Enviromental differences in gentamicin pharmacokinetics by using population pharmacokinetic methods were compared with 20 Korean patients and 24 Korean-American appendicitis patients. Two to six blood specimens were collected from all patients at the following times : just before a regularly scheduled infusion and at 0.5 hour after the end of a 0.5 hour infusion. Nonparametric expected maximum (NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant (K), the slope (KS) of the relationship between K versus creatinine clearance ($C_{cr}$), the apparent volume of distribution (V), the slope (VS) of the relationship between V versus weight, gentamicin clearance (CL) and the slope (CS) of the relationship between CL versus $C_{cr}$ and the V. The output includes two marginal probability density function (PDF), means, medians, modes, variance and CV%. The mean K (KS) were $0.402{\pm}0.129\;h^{-1}(0.00486{\pm}0.00197\;[h{\cdot}ml/min/1.73\;m^2]^{-1})$ and $0.411{\pm}0.135\;h^{-1}(0.00475{\pm}0.00180\;[h{\cdot}ml/min/1.73\;m^2]^{-1})$ for Korean and Korean-American populations, respectively. The mean V (VS) were not different at $14.3{\pm}3.6l(0.241{\pm}0.0511l/kg)$ and $15.1{\pm}3.84l(0.239{\pm}0.0492l/kg)$ for Korean and Korean-American populations, respectively (p>0.2). The mean CL (CS) were $5.68{\pm}1.69l/h(0.0714{\pm}0.0222l/kg[h{\cdot}ml/min/1.73\;m^2])$ and $5.70{\pm}1.77l/h(0.0701{\pm}0.0215l/kg[h{\cdot}ml/min/1.73\;m^2])$ for Korean and Korean-American populations, respectively. There were no enviromental differences in gentamicin pharmacokinetics between Korean and Korean-American appendicitis patients.

Keywords

References

  1. Sheiner, B. B., Beal, S., Rosenberg, B. and Marathe, V. V. : Forecasting individual pharmacokinetics. Clin. Pharmacol. Ther. 31, 294 (1979).
  2. Hurst, A., Yoshinaga, M., Mitani, G., Foo, K., Jelliffe, R. W. and Harrison, E. : Application of a bayesian method to monitor and adjust vancomycin dosage regimens. Antimicrob. Agents Chemother. 34, 1165 (1990).
  3. Touw, D. J., Proost, J. H., Stevens, R., Lafeber, H. N. and van Weissenbruch, M. M. : Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus. Pharm. World Sci. 23, 200 (2001).
  4. Nielsen, E. I., Sandstrom, M., Honore, P. H., Ewald, U. and Friberg, L. E. : Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study. Clin. Pharmacokinet. 48, 253 (2009).
  5. Seaton, C., Ignas, J., Muchohi, S., Kokwaro, G., Maitland, K. and Thomson, A. H. : Population pharmacokinetics of a single daily intramuscular dose of gentamicin in children with severe malnutrition. J. Antimicrob. Chemother. 59, 681 (2007).
  6. Garcia, B., Barcia, E., Perez, F. and Molina, I. T. : Population pharmacokinetics of gentamicin in premature newborns. J. Antimicrob. Chemother. 58, 372 (2006).
  7. Xuan, D., Nicolau, D. P. and Nightingale, C. H. : Population pharmacokinetics of gentamicin in hospitalized patients receiving once-daily dosing. Int. J. Antimicrob. Agents 23, 291 (2004).
  8. Treluyer, J. M., Merle, Y., Tonnelier, S., Rey, E. and Pons, G. : Nonparametric population pharmacokinetic analysis of amikacin in neonates, infants, and children. Antimicrob. Agents Chemother. 46, 1381 (2002).
  9. Biggeri, A., Marchi, M., Lagazio, C., Martuzzi, M. and Bohning, D. : Non-parametric maximum likelihood estimators for disease mapping. Stat. Med. 15, 2539 (2000).
  10. Bustad, A., Terziivanov, D., Leary, R., Port, R., Schumitzky, A. and Jelliffe, R. : Parametric and nonparametric population methods: their comparative performance in analysing a clinical dataset and two Monte Carlo simulation studies. Clin. Pharmacokinet. 45, 365 (2006).
  11. Stolk, L. M., Degraeuwe, P. L., Nieman, F. H., de Wolf, M. C. and de Boer, A. : Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates. Ther. Drug. Monit. 24, 527 (2002).
  12. Rougier, F., Claude, D., Maurin, M., Sedoglavic, A., Ducher, M., Corvaisier, S., Jelliffe, R. and Maire, P. : Aminoglycoside nephrotoxicity: modeling, simulation, and control. Antimicrob. Agents Chemother. 47, 1010 (2003).
  13. Garrison, M. W., Zaske, D. E. and Rotschafer, J. C. : Aminoglycosides: another perspective. Ann. Pharmacother. 24, 267 (1990).
  14. Burm, J. P. : The influence of weight with assay error on gentamicin pharmacokinetics using the Bayesian and nonlinear least square regression analysis in appendicitis patients. Biopharm. Drug Dispos. 26, 189 (2005).
  15. Jelliffe, R. W., D'Argenio, D. Z., Schumitzky, A., Hu, L. and Liu, M. : The $USC^*$PACK PC programs for planning, monitoring and adjusting drug dosage regimens. Proceedings of the twenty-third annual meeting of the Association for the Advancement of Medical Instrumentation. Washington, DC, May, p. 13 (1988).
  16. Press, S. J. : Bayesian statistics: Principles, models, and application. John Wiley & Sons, Inc., Appendices 1-4, p. 175 (1989).
  17. Jelliffe, R. W. and Schumitzky, A. : User manual for the nonparametric EM program for population pharmacokinetic modeling version 1. University of Southern California, School of Medicine, Los Angeles, Calfornia (1989).
  18. Sawchuk, R. J. and Zaske, D. E. : Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients. J. Pharmacokinet. Biopharm. 4, 183 (1976).
  19. Vercaigne, L. M., Ariano, R. E. and Zacharias, J. M. : Bayesian pharmacokinetics of gentamicin in a haemodialysis population. Clin. Pharmacokinet. 43, 205 (2004).
  20. Jelliffe, R. W., Iglesias, T., Hurst, A., Foo, K. and Rodriguez, J. : Individualizing gentamicin dosage regimens. A comparative review of selected models, data fitting methods and monitoring stategies. Clin. Pharmacokinet. 21, 461 (1991).
  21. Erdmann, S. M., Rodvold, K. A. and Pryka, R. D. : An updated comparison of drug dosing methods. Part III: amionglycoside antibiotics. Clin. Pharmacokinet. 20, 374 (1991).
  22. Thomson, A. H. and Whiting, B : Bayesian parameter estimation and population pharmacokinetics. Clin. Pharmacokinet. 22, 447 (1992).
  23. Jelliffe, R. W., Schumitzky, A. and Van Guilder, M. : Nonpharmacokinetic factors affecting aminoglycoside therapeutic precision: A simulation study. Drug Invest. 4, 20 (1992).
  24. Antal, E. J., Grasela, T. H. and Smith, R. B. : An evaluation of population pharmacokinetics in therapeutic trials. Part III: prospective data collection versus retrospective data assembly. Clin. Pharmacol. Ther. 46, 552 (1989).
  25. Gan, S. H., Ismail, R., Wan Adnan, W. A., Zulmi, W. and Jelliffe, R. W. : Population pharmacokinetic modelling of tramadol with application of the NPEM algorithms. J. Clin. Pharm. Ther. 29, 455 (2004).
  26. Beal, S. : Population pharmacokinetic data and parameter estimation based on their first two statistical moments. Drug Metab. Rev. 16, 173 (1984).
  27. Beal, S. : Asymptotic properties of optimization estimates for the independent net identically distributed case with application to extended least-squares estimate. Technical report of the Division of Clinical Pharmacology. University of Califormia, San Francisco (1984).
  28. Mallet, A. : A maximum likelihood estimation method for random coefficient regression models. Biometrika 73, 645 (1986).
  29. Mallet, A., Mentre, F., Steimer, J. L. and Lookiec, F. : Nonparametric maxmum likelihood estimation for population pharmacokinetics with application to cyclosporine. J. Pharmacokinet. Biopharm. 16, 311 (1988).
  30. Dodge, W. F., Jelliffe, R. W., Richardson, C. J. and McCleery, R. A. : Gentamicin population pharmacokinetic models for low birth weight infants using a new nonparametric method. Clin. Pharmacol. Ther. 50, 25 (1991).
  31. Bond, W. S. : Ethnicity and psychotropic drugs. Clin. Pharm. 10, 467 (1991).
  32. Wood, A. and Zhou, H. : Ethnic differences in drug disposition and responsiveness. Clin. Pharmacokinet. 20, 350 (1991).
  33. Jhee, S. S., Burm, J. P. and Gill, M. A. : Comparison of aminoglycoside pharmacokinetics in asian, hispanic and caucasian patient using population pharmacokinetic methods. Antimicrob. Agents Chemother. 38, 2073 (1994).
  34. Botha, J. H., du Preez, M. J. and Adhikari, M. : Population pharmacokinetics of gentamicin in South African newborns. Eur. J. Clin. Pharmacol. 59. 755 (2003).