Saliva as a specimen for monitoring compliance but not for predicting plasma concentrations in patients with HIV treated with indinavir

The presence of the HIV-protease inhibitor indinavir in saliva was analyzed to investigate whether salivary indinavir concentrations are applicable to monitor compliance and/or predict plasma indinavir levels. Fourteen HIV-in fected outpatients treated with indinavir and 24 healthy volunteers who ing ested a single dose of indinavir were included. Paired plasma and citric-ac id-stimulated saliva samples were analyzed by high-performance liquid chrom atography (HPLC). Stimulated salivary indinavir concentrations showed a hig h correlation (r = 0.85, p < 0.01) with corresponding plasma levels. The me dian saliva/plasma ratio was 65% (P-25 50%; P-75 94%). The ratios were inde pendent of the plasma concentration; however, a relation with time after in gestion was seen. The unbound fraction of indinavir in plasma was not signi ficantly correlated with the saliva/plasma ratio after stimulated saliva co llection, in contrast with a subset of nonstimulated saliva from healthy vo lunteers, where we did find a significant correlation. Although stimulated salivary indinavir concentrations are highly correlated with plasma concent rations, it is not possible to predict plasma indinavir levels by the saliv ary concentrations for purposes of therapeutic drug monitoring, due to larg e interindividual and intraindividual variation. Nevertheless, monitoring c ompliance by measuring the presence of indinavir in saliva is possible: ing estion of indinavir can be assessed with a sensitivity of 84.8% in the whol e dosing interval or with 98.8% between 1 and 6 hours after the last dose, which is comparable with plasma.