Pharmacokinetics of Lopinavir/Ritonavir: Changes Across Formulations and Ages

Role of Highly-Active Antiretroviral Therapy
Role of Highly-Active Antiretroviral Therapy
Dosing recommendations for lopinavir/ritonavir include larger doses for infants; this may still result in low drug concentrations for infants younger than 6 months of age receiving the liquid formulation.

Although dosing recommendations for lopinavir/ritonavir include larger doses for infants to account for higher apparent clearance, data demonstrate that this may still result in low lopinavir concentrations for infants younger than 6 months receiving the liquid formulation, according to a population pharmacokinetic analysis published in the Journal of Clinical Pharmacology.1

Lopinavir is recommended as part of a first-line antiretroviral regimen in pediatric patients, and is available in a liquid formulation that may be used in infants as young as 2 weeks of age.2 Ritonavir is a pharmacokinetic enhancer and is coformulated with lopinavir in 3 distinct formulations: liquid, soft gel capsule, and melt-extrusion tablet. Although there are several studies that describe lopinavir/ritonavir pharmacokinetics in adults and children,3-10 no studies have described the dynamic changes that occur with lopinavir/ritonavir from infancy to adulthood. 

Therefore, researchers performed a composite population pharmacokinetic analysis using 6 pediatric and adult studies performed in 297 patients aged 6 weeks to 63 years receiving the 3 different formulations.1 They found that when using the World Health Organization weight-band dosing recommendations, patients younger than 6 months had a lower area under the drug concentration-time curve (94.8 vs >107.4 µg hour/mL) and minimum observed concentration of drug in blood plasma values (5.0 vs >7.1 µg/mL) compared with older children and adults. In addition, an increase in bioavailability was observed with the transition from liquid to tablet formulation.

The researchers concluded that “the [World Health Organization] weight-band dosing simulation shows potential for low [lopinavir] concentration in early infancy with currently recommended dosing and may require further evaluation for improved dosing recommendations adjusted for newly available [lopinavir/ritonavir] pediatric formulations such as sprinkles.”1

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  2. National Institutes of Health Guidelines for the use of antiretroviral agents in pediatric HIV infection. Accessed January 2, 2018.
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