SALIVARY DRUG-MONITORING OF IRINOTECAN AND ITS ACTIVE METABOLITE IN CANCER-PATIENTS

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 mali gnancies who received 60 mg/m(2) CPT-11 (21 courses). Plasma and unsti mulated whole saliva were collected over a 24-h period, and concentrat ions of CPT-11 and SN-38 were measured by high-performance liquid chro matography. Both CPT-11 and SN-38 were detectable in saliva, and the c oncentration-time curves in plasma and saliva showed a very similar pa ttern. A good correlation was observed between the saliva concentratio n (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 und er the concentration-time curve calculated for saliva (AUC(s)) correla ted 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 plasm a for pharmacokinetics/pharmacodynamics studies of CPT-11.