Can Saliva Be Used For Therapeutic Drug Monitoring Of Protease Inhibitors In Hiv-Infected Children?

Purpose HIV-infected children may become a target category for therapeutic drug monitoring (TDM) of antiretroviral therapy (ART) due to the unpredictability of plasma concentrations. Studies suggest that saliva could be used instead of blood for TDM. This has distinct advantages in pediatrics as saliva sampling is painless and prevents blood loss. The purpose of this study was to determine the total concentrations of lopinavir and ritonavir in plasma of children with HIV infection and compare them with the total saliva concentration. Methods 15 pediatric patients (median age 8.9 years) receiving combination ART were enrolled. Unbound lopinavir and ritonavir were separated by ultrafiltration. The drug serum and saliva concentrations were determined by a tandem-mass spectrometric method using Sciex APT-2000. Routine statistical methods were used to examine the relation between total drug plasma and saliva concentrations. Results The relation between total saliva and serum concentrations of lopinavir and ritonavir were highly significant with r values of 0.991 for ritonavir (RittotalSal = 0.043×RittotalPl+108.7, p<0.001) and 0.993 for lopinavir (LoptotalSal = 0.019×LoptotalPl-59.26, p<0.0001). Conclusion This pilot study demonstrated a significant linear correlation between total saliva and serum concentrations of lopinavir and ritonavir. The measurement of concentrations of these drugs in saliva may be useful for application of TDM of PIs in pediatric patients. Clinical Pharmacology & Therapeutics (2004) 75, P73–P73; doi: 10.1016/j.clpt.2003.11.275