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Posaconazole

Posaconazole is an antifungal agent that is administered orally. It is available as a tablet and liquid suspension. The suspension has a lower relative bioavailability and the extent of absorption is decreased by concomitant use of proton pump inhibitors and by diarrhoea.

The population pharmacokinetics of posaconazole have been described in children by (Boonsathorn, Cheng et al. 2019). Theory based allometry and standardization to body mass of 70 kg allows extrapolation to adults.

Target Concentration

The recommended target concentration for treatment is an average steady state concentration of 1.25 mg/L or a steady state trough of 1 mg/L with an 8 h dosing interval. A lower steady state trough concentration of 0.7 mg/L is recommended for prophylaxis (Ashbee, Barnes et al. 2014). The average steady state treatment target comes from an exploratory analysis of the association between exposure metrics and clinical response (Figure 1) (Walsh, Raad et al. 2007).

Figure 1 Exposure response (Walsh, Raad et al. 2007)

Figure 1 Posaconazole oral tablet

There is no effect of diarrhoea (DIA), proton pump inhibitors (PPI) on bioavailability (F).

References

Ashbee, H. R., R. A. Barnes, E. M. Johnson, M. D. Richardson, R. Gorton and W. W. Hope (2014). "Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology." J Antimicrob Chemother 69(5): 1162-1176.

Boonsathorn, S., I. Cheng, F. Kloprogge, C. Alonso, C. Lee, B. Doncheva, J. Booth, R. Chiesa, A. Irwin and J. F. Standing (2019). "Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children." Clin Pharmacokinet 58(1): 53-61.

Walsh, T. J., I. Raad, T. F. Patterson, P. Chandrasekar, G. R. Donowitz, R. Graybill, R. E. Greene, R. Hachem, S. Hadley, R. Herbrecht, A. Langston, A. Louie, P. Ribaud, B. H. Segal, D. A. Stevens, J.-A. H. van Burik, C. S. White, G. Corcoran, J. Gogate, G. Krishna, L. Pedicone, C. Hardalo and J. R. Perfect (2007). "Treatment of Invasive Aspergillosis with Posaconazole in Patients Who Are Refractory to or Intolerant of Conventional Therapy: An Externally Controlled Trial." Clinical Infectious Diseases 44(1): 2-12.