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Assessment of lopinavir pharmacokinetics with respect to developmental changes in infants and the impact on weight

M Nikanjam1, E G Chadwick, B Robbins

  • 1University of California, San Diego, La Jolla, California, USA.

Clinical Pharmacology and Therapeutics
|December 23, 2011
PubMed

Insights

New dosing guidelines for lopinavir/ritonavir (LPV/r) in infants are effective. World Health Organization weight band dosing ensures therapeutic drug levels in HIV-infected infants, comparable to FDA-recommended regimens.

Area of Science:

  • Pediatric infectious diseases
  • Pharmacology and toxicology
  • HIV/AIDS therapeutics

Background:

  • Antiretroviral therapies are crucial for HIV-infected infants due to rapid disease progression.
  • Perinatal exposure to antiretrovirals can lead to drug resistance in infants.
  • Optimized dosing of lopinavir/ritonavir (LPV/r) is needed for this vulnerable population.

Purpose of the Study:

  • To characterize the population pharmacokinetics (PK) of lopinavir (LPV) in HIV-infected infants.
  • To assess LPV/r dosing requirements based on maturational changes in infants.
  • To investigate the relationship between LPV PK and viral dynamics.

Main Methods:

  • Longitudinal pharmacokinetic data from a clinical trial of LPV/r in infants (<6 months of age) were analyzed.
  • Population PK analysis was performed using NONMEM software.
  • Monte Carlo simulations were used to evaluate dosing recommendations.

Main Results:

  • Infant LPV PK was characterized by high apparent clearance (CL/F) that decreased with age.
  • Age and ritonavir concentrations were significant covariates influencing LPV PK.
  • Lower initial LPV concentrations in younger infants did not correlate with viral dynamics.
  • WHO weight band-based dosing predicted therapeutic LPV concentrations.

Conclusions:

  • WHO weight band-based dosing for LPV/r in infants achieves therapeutic drug exposure.
  • These recommendations provide drug exposure levels comparable to FDA-suggested regimens.
  • This supports the use of WHO weight band dosing for optimizing LPV/r therapy in young HIV-infected infants.

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