This secondary analysis explored changes in protein-unbound concentrations of lopinavir and amprenavir when co-administered in HIV-infected subjects. Total and unbound pharmacokinetic parameters were calculated and compared between subjects receiving each agent alone, and co-administration. When co-administered, unbound and total concentrations decrease. Co-administration significantly increased lopinavir unbound clearance, while significant changes in fraction unbound (fu) were not detected. For amprenavir, significant increases in fu and unbound clearance occurred with co-administration. This demonstrates the complex nature of drug-drug interactions between highly protein-bound, CYP-metabolized drugs, and the need to measure unbound concentrations in disease states like hepatitis C, where such agents are co-administered
