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Model-based approach for optimization of atazanavir dose recommendations for HIV-infected pediatric patients

Ying Hong1, Kenneth G Kowalski, Jenny Zhang

  • 1Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA.

Antimicrobial Agents and Chemotherapy
|September 21, 2011
PubMed

Insights

This study recommends body weight-based atazanavir (Reyataz; ATV) capsule doses for pediatric HIV patients. Model-based simulations ensure pediatric exposures match adult levels when using ATV with ritonavir (RTV).

Area of Science:

  • Pharmacology
  • Pediatric HIV Treatment
  • Pharmacokinetics

Background:

  • Atazanavir (ATV) is a potent, well-tolerated protease inhibitor for HIV treatment.
  • Its favorable profile makes it suitable for pediatric HIV patients.
  • Optimizing pediatric dosing is crucial for effective treatment.

Purpose of the Study:

  • To recommend body weight-based atazanavir capsule doses for pediatric patients.
  • To ensure pharmacokinetic exposure in children mirrors that in adults.
  • To utilize a model-based approach for dose recommendations.

Main Methods:

  • A C(0)-delinked one-compartment model described ATV concentration-time data from adult and pediatric studies.
  • Pharmacokinetic parameters (CL/F, V/F) were analyzed in relation to body weight.
  • Model-based simulations informed dose recommendations for pediatric populations.

Main Results:

  • Apparent clearance (CL/F) and volume of distribution (V/F) increased with body weight.
  • Ritonavir (RTV) comedication reduced CL/F by 40.9% but increased relative bioavailability (F(rel)) by 132%.
  • The ATV powder formulation had 35.5% lower bioavailability than the capsule.

Conclusions:

  • Recommended weight-based ATV capsule doses (150-300 mg) boosted with RTV (100 mg) for pediatric patients ≥15 kg.
  • These doses aim to achieve exposures comparable to adults on standard ATV/RTV therapy.
  • This provides a guideline for optimizing pediatric HIV treatment with atazanavir.

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