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External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models.

Publication ,  Journal Article
Hwang, MF; Beechinor, RJ; Wade, KC; Benjamin, DK; Smith, PB; Hornik, CP; Capparelli, EV; Duara, S; Kennedy, KA; Cohen-Wolkowiez, M; Gonzalez, D
Published in: Antimicrob Agents Chemother
December 2017

Fluconazole is an antifungal agent used for the treatment of invasive candidiasis, a leading cause of morbidity and mortality in premature infants. Population pharmacokinetic (PK) models of fluconazole in infants have been previously published by Wade et al. (Antimicrob Agents Chemother 52:4043-4049, 2008, https://doi.org/10.1128/AAC.00569-08) and Momper et al. (Antimicrob Agents Chemother 60:5539-5545, 2016, https://doi.org/10.1128/AAC.00963-16). Here we report the results of the first external evaluation of the predictive performance of both models. We used patient-level data from both studies to externally evaluate both PK models. The predictive performance of each model was evaluated using the model prediction error (PE), mean prediction error (MPE), mean absolute prediction error (MAPE), prediction-corrected visual predictive check (pcVPC), and normalized prediction distribution errors (NPDE). The values of the parameters of each model were reestimated using both the external and merged data sets. When evaluated with the external data set, the model proposed by Wade et al. showed lower median PE, MPE, and MAPE (0.429 μg/ml, 41.9%, and 57.6%, respectively) than the model proposed by Momper et al. (2.45 μg/ml, 188%, and 195%, respectively). The values of the majority of reestimated parameters were within 20% of their respective original parameter values for all model evaluations. Our analysis determined that though both models are robust, the model proposed by Wade et al. had greater accuracy and precision than the model proposed by Momper et al., likely because it was derived from a patient population with a wider age range. This study highlights the importance of the external evaluation of infant population PK models.

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Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

December 2017

Volume

61

Issue

12

Location

United States

Related Subject Headings

  • Predictive Value of Tests
  • Models, Statistical
  • Microbiology
  • Male
  • Infant, Premature
  • Infant, Newborn
  • Infant
  • Humans
  • Fluconazole
  • Female
 

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Hwang, M. F., Beechinor, R. J., Wade, K. C., Benjamin, D. K., Smith, P. B., Hornik, C. P., … Gonzalez, D. (2017). External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models. Antimicrob Agents Chemother, 61(12). https://doi.org/10.1128/AAC.01352-17
Hwang, Michael F., Ryan J. Beechinor, Kelly C. Wade, Daniel K. Benjamin, P Brian Smith, Christoph P. Hornik, Edmund V. Capparelli, et al. “External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models.Antimicrob Agents Chemother 61, no. 12 (December 2017). https://doi.org/10.1128/AAC.01352-17.
Hwang MF, Beechinor RJ, Wade KC, Benjamin DK, Smith PB, Hornik CP, et al. External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models. Antimicrob Agents Chemother. 2017 Dec;61(12).
Hwang, Michael F., et al. “External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models.Antimicrob Agents Chemother, vol. 61, no. 12, Dec. 2017. Pubmed, doi:10.1128/AAC.01352-17.
Hwang MF, Beechinor RJ, Wade KC, Benjamin DK, Smith PB, Hornik CP, Capparelli EV, Duara S, Kennedy KA, Cohen-Wolkowiez M, Gonzalez D. External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models. Antimicrob Agents Chemother. 2017 Dec;61(12).

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

December 2017

Volume

61

Issue

12

Location

United States

Related Subject Headings

  • Predictive Value of Tests
  • Models, Statistical
  • Microbiology
  • Male
  • Infant, Premature
  • Infant, Newborn
  • Infant
  • Humans
  • Fluconazole
  • Female