Share This Article:

Effects of Obesity on Posaconazole Kinetics in a Patient with Graft versus Host Disease

Abstract Full-Text HTML XML Download Download as PDF (Size:149KB) PP. 244-247
DOI: 10.4236/pp.2013.42034    3,746 Downloads   6,042 Views   Citations

ABSTRACT

Posaconazole, a triazole antifungal agent, displays a highly variable pharmacokinetic profile due in part to the oral solution, the only currently available dosage form. Posaconazole activity appears to be dose-dependent and clinical outcomes correlate with steady-state serum trough concentrations and area under the concentration curve (AUC) over minimum inhibitory concentration (MIC) ratios. Therapeutic drug monitoring (TDM) has been recommended to help overcome the unpredictable nature of the drug. The impact of obesity of posaconazole pharmacokinetics and the use of TDM in this population has not been well described; however, limited data demonstrate increased weight correlates with lower serum concentrations and reduced drug exposure. We describe the use of TDM in an obese man, 12 months status post hematopoietic stem-cell transplant (HSCT), receiving posaconazole therapy for a presumed invasive fungal infection (IFI).

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

J. Pettis, S. Hyche, K. Logan, A. Poursina and P. Bookstaver, "Effects of Obesity on Posaconazole Kinetics in a Patient with Graft versus Host Disease," Pharmacology & Pharmacy, Vol. 4 No. 2, 2013, pp. 244-247. doi: 10.4236/pp.2013.42034.

References

[1] CDC Centers for Disease Control and Prevention, “Overweight and Obesity,” 2012. http://www.cdc.gov/obesity/data/facts.html
[2] M. J. Hanley, D. R. Abernethy and D. J. Greenblatt, “Effect of Obesity on the Pharmacokinetics of Drugs in Humans,” Clinical Pharmacokinetics, Vol. 49, No. 2, 2010, pp. 71-87. doi:10.2165/11318100-000000000-00000
[3] D. Andes, K. Marchillo, R. Conklin, et al., “Pharmacodynamics of a New Triazole, Posaconazole, in a Murine Model of Disseminated Candidiasis,” Antimicrobial Agents and Chemotherapy, Vol. 48, No. 1, 2004, pp. 137-142. doi:10.1128/AAC.48.1.137-142.2004
[4] Y. Li, U. Theuretzbacher, C. J. Clancy, M. H. Nguyen and H. Derendorf, “Pharmacokinetic/Pharmacodynamic Profile of Posaconazole,” Clinical Pharmacokinetics, Vol. 49, No. 6, 2010, pp. 379-396. doi:10.2165/11319340-000000000-00000
[5] S. J. Howard, T. W. Felton, A. Gomez-Lopez and W. W. Hope, “Posaconazole: The Case for Therapeutic Drug Monitoring,” Therapeutic Drug Monitoring, Vol. 34, No. 1, 2012, pp. 72-76. doi:10.1097/FTD.0b013e31823cdeac
[6] M. J. Dolton, J. E. Ray, D. Marriott and A. J. McLachlan, “Posaconazole Exposure-Response Relationship: Evaluating the Utility of Therapeutic Drug Monitoring,” Antimicrobial Agents and Chemotherapy, Vol. 56, No. 6, 2012, pp. 2806-2813. doi:10.1128/AAC.05900-11
[7] R. Courtney, S. Pai, M. Laughlin, J. Lim and V. Batra, “Pharmacokinetics, Safety, and Tolerability of Oral Posaconazole Administered in Single and Multiple Doses in Healthy Adults,” Antimicrobial Agents and Chemotherapy, Vol. 47, No. 9, 2003, pp. 2788-2795. doi:10.1128/AAC.47.9.2788-2795.2003
[8] S. Kuipers, R. J. M. Brüggemann, R. G. L. de Sévaux, et al., “Failure of Posaconazole Therapy in a Renal Transplant Patient with Invasive Aspergillosis Due to Aspergillus fumigatus with Attenuated Susceptibility to Posaconazole,” Antimicrobial Agents and Chemotherapy, Vol. 55, No. 7, 2011, pp. 3564-3566. doi:10.1128/AAC.01544-10
[9] R. Wurtz, G. Itokazu and K. Rodvold, “Antimicrobial Dosing in Obese Patients,” Clinical Infectious Diseases, Vol. 25, No. 1, 1997, pp. 112-118. doi:10.1086/514505
[10] T. J. Walsh, I. Raad, T. J. Patterson, et al., “Treatment of Invasive Aspergillosis with Posaconazole in Patients who Are Refractory to or Intolerant of Conventional Therapy: An Externally Controlled Trial,” Clinical Infectious Diseases, Vol. 44, No. 1, 2007, pp. 2-12. doi:10.1086/508774
[11] S. H. Jang, P. M. Colangelo and J. V. Gobburu, “Exposure-Response of Posaconazole Used for Prophylaxis against Invasive Fungal Infections: Evaluating the Need to Adjust Doses Based on Drug Concentrations in Plasma,” Clinical Pharmacology & Therapeutics, Vol. 88, 2010, pp. 115-119. doi:10.1038/clpt.2010.64
[12] E. Mavridou, R. J. Bruggemann, W. J. Melchers, J. W. Mouton and P. E. Verweij, “Efficacy of Posaconazole against Three Clinical Aspergillus fumigatus Isolates with Mutations in the CYP51A Gene,” Antimicrobial Agents and Chemotherapy, Vol. 54, No. 2, 2010, pp. 860-865. doi:10.1128/AAC.00931-09
[13] S. J. Howard, J. M. Lestner, A. Sharp, L. Gregson, J. Goodwin, J. Slater, J. B. Majithiya, P. A. Warn and W. W. Hope, “Pharmacokinetics and Pharmacodynamics of Posaconazole for Invasive Pulmonary Aspergillosis: Clinical Implications for Antifungal Therapy,” The Journal of Infectious Diseases, Vol. 203, No. 9, 2011, pp. 1324-1332. doi:10.1093/infdis/jir023
[14] R. K. Shields, C. J. Clancy, A. Vadnerkar, et al., “Posaconazole Serum Concentrations among Cardiothoracic Transplant Recipients: Factors Impacting trough Levels and Correlation with Clinical Response to Therapy,” Antimicrobial Agents and Chemotherapy, Vol. 55, No. 3, 2011, pp. 1308-1311. doi:10.1128/AAC.01325-10
[15] G. Krishna, M. Martinho, P. Chandrasekar, A. J. Ullmann and H. Patino, “Pharmacokinetics of Oral Posaconazole in Allogeneic hematopoietic Stem Cell Transplant Recipients with Graft-versus-Host Disease,” Pharmacotherapy, Vol. 27,No. 12, 2007, pp. 1627-1636.
[16] G. Krishna, L. Ma, M. Martinho, R. A. Preston and E. O’Mara, “A New Solid Oral Tablet Formulation of Posaconazole: A Randomized Clinical Trial to Investigate Rising Singleand Multiple-Dose Pharmacokinetics and Safety in Healthy Volunteers,” Journal of Antimicrobial Chemotherapy, Vol. 67, No. 11, 2012, pp. 2725-2730. doi:10.1093/jac/dks268

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.