Salivary drug monitoring of irinotecan and its active metabolite in cancer patients

Abstract

 To assess the clinical usefulness of salivary monitoring of irinotecan (CPT-11) and its active metabolite (SN-38), we examined the clinical pharmacological profile of both drugs in 9 patients with thoracic malignancies who received 60 mg/m² CPT-11 (21 courses). Plasma and unstimulated whole saliva were collected over a 24-h period, and concentrations of CPT-11 and SN-38 were measured by high-performance liquid chromatography. Both CPT-11 and SN-38 were detectable in saliva, and the concentration-time curves in plasma and saliva showed a very similar pattern. A good correlation was observed between the saliva concentration (C_s) and the plasma concentration (C_p) for both CPT-11 and SN-38 (r=0.732, P<0.0001 and r = 0.611, P<0.0001, respectively). The area under the concentration-time curve calculated for saliva (AUC_s) correlated with that generated for plasma (AUC_p) for both CPT-11 and SN-38 (r = 0.531, P = 0.012 and r = 0.611, P = 0.0025, respectively). These results suggest that it may be feasible to use saliva instead of plasma for pharmacokinetics/pharmacodynamics studies of CPT-11.