Lopinavir/Ritonavir (Kaletra) PK in Children
Condition: HIV/AIDS Treatment; HIV Infections
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      The objective of this study is to compare the pharmacokinetics of lopinavir tablets
      administered to pediatric patients as either whole or crushed tablets. The study is a
      randomized,open-label, crossover study of pediatric subjects already taking
      lopinavir/ritonavir tablets as part of their clinical care. THe investigators hypothesize
      that lopinavir exposure in pediatric patients will be lower after taking a dose of the tablet
      formulation, crushed and mixed with pudding or yogurt, as compared to the exposure after
      taking a dose with tablets swallowed whole.
    

Detailed description: 
      By the end of 2005, approximately 2.3 million children worldwide were living with HIV/AIDS.1
      At least 660,000 children worldwide have advanced HIV/AIDS and are in dire need of
      antiretroviral treatment. While many barriers exist to scaling up HIV/AIDS care and treatment
      globally, access to life-saving treatments for children is increasing. The protease
      inhibitor, lopinavir/ritonavir (Kaletra®), is recommended as a first-line agent by the World
      Health Organization and by the US Department of Health and Human Services for the treatment
      of pediatric patients in resource-limited settings and in the United States.

      The prescribing information states that these tablets may not be crushed, broken or chewed,
      and the manufacturer does not plan to examine the pharmacokinetics of crushed tablets at this
      time. The company found that the crushed tablets were poorly absorbed in a small
      pharmacokinetic study in several dogs. While this information has spread through
      investigators by word-of-mouth, this information has not been published in any forum by the
      company, and no guidance as to the extent of the decrease in absorption has been provided.
      However, patients and caregivers are dosing pediatric patients with crushed tablets to
      overcome some of the limitations of the oral solution. If crushed tablet administration
      yields significantly lower systemic exposure to lopinavir than whole tablets, then patients
      using this administration technique will be at higher risk for development of viral
      resistance and treatment failure. This administration technique must be studied so that
      providers have evidence to support recommendations about this dose administration strategy.
    

Intervention name(s): lopinavir/ritonavir (Kaletra®) tablets
Intervention type(s): Drug
Intervention description(s): The subject will bring their own prescription of lopinavir/ritonavir. The patient will take a witnessed dose of lopinavir/ritonavir with an 6 ounce glass of cool water (if taken whole) or mixed in 4 ounces of Jell-O brand pudding (if crushed).
Other intervention name(s): Kaletra®
Intervention MeSH terms: Ritonavir; Lopinavir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV/AIDS; pediatrics; resource-limited settings; lopinavir; ritonavir; Kaletra®; antiretroviral treatment; crushed tablets; treatment experienced