PRELIMINARY PHARMACOKINETICS OF A NEW ANTHELMINTIC AGENT, CDRI-81 470IN HEALTHY-SUBJECTS/

Single dose pharmacokinetic study of CDRI-81/470, a new broad spectrum anthelmintic agent, was carried out in 12 healthy human subjects afte r a single 375-mg oral dose. The serum, saliva and urine samples were analyzed by HPLC. The compound attained peak serum levels of 15.1 +/- 4.6 mu g/ml in 2.6 +/- 1.1 h and could be measured up to 5 days. Mean serum AUC was 195 +/- 69 mu g per h/ml. The compound showed a mean app arent elimination half-life of 12.1 +/- 4.5 h while mean residence tim e (MRT) was found to be 11.1 +/- 1.7 h. Extent of urinary excretion of CDRI-81/470 (2.3 +/- 0.7%) was less than that of its decarboxylate me tabolite (5.3 +/- 2.2%) up to 10 h post dose. In vivo protein binding in serum was 93.1 +/- 1.2% and remained constant over in vivo concentr ation range. The salivary levels of CDRI-81/470 were higher than the c orresponding unbound serum levels. There was a significant correlation between serum and salivary levels of CDRI-81/470, with a mean ratio o f saliva to unbound serum levels of 2.04 +/- 0.24, indicating the poss ibility of predicting serum concentrations of CDRI-81/470 from non-inv asive salivary sampling technique. (C) 1998 Elsevier Science B.V. All rights reserved.