EFFECTS OF CIGARETTE-SMOKE INHALATION ON PLASMA DILTIAZEM LEVELS IN RATS

A rapid and sensitive method for the assay of plasma diltiazem was dev eloped using a solid-phase extraction technique followed by high-perfo rmance liquid chromatography. The effects of cigarette smoke on plasma levels of orally administered diltiazem was investigated in rats. The animals were exposed to cigarette smoke for 10 min using a Hamburg II smoking machine, immediately after oral administration of diltiazem ( 10 mg/kg). In the nonsmoking nonrestrained rats, plasma diltiazem leve ls increased rapidly and reached the maximum (7.1 mu g/kg) 2 h after a dministration and decreased gradually thereafter. In the nonsmoking re strained rats, plasma diltiazem levels increased rapidly, but showed a lmost constant levels between 1 h and 8 h after administration. The ma ximum level (5.4 mu g/kg) was shown after 2 h. On the other hand, plas ma diltiazem levels in the rats exposed to cigarette smoke reached the maximum (4.3 mu g/kg) after 4 h. These results suggest that absorptio n of orally administered diltiazem is inhibited and delayed by cigaret te smoke.