DETERMINATION OF SERUM DILTIAZEM CONCENTRATIONS IN A PHARMACOKINETIC STUDY USING GAS-CHROMATOGRAPHY WITH ELECTRON-CAPTURE DETECTION

An open cross-over randomized clinical trial was performed in nine healthy humans to determine steady-state pharmacokinetics and bioavailability of three oral diltiazem preparations, tablets containing 60 and 90 mg of diltiazem hydrochloride, administered in total daily doses of 180 mg. Serum drug levels were determined by gas chromatography with electron capture detection following a simple extraction procedure. Blood samples were collected before and at several post-dosing intervals after administration of the last dose in steady state, and pharmacokinetic parameters were calculated. The steady-state diltiazem concentrations in sera were determined 48 h after the first dose, and were (mean +/- SD): 46.4 +/- 28.1, 60.8 +/- 36.3 and 36.8 +/- 22.6-mu-g l-1 for Pliva 90, and Aldizem 90 diltiazem preparations, respectively. The corresponding elimination half-lives were 5.6 +/- 2.0, 5.2 +/- 1.8 and 6.9 +/- 3.2 h; peak concentrations were 88.4 +/- 29.5, 153.5 +/- 86.5 and 139.2 +/- 72.5-mu-g l-1, and areas under the concentration curves (AUC 12 h) were 477.4 +/- 172.5, 989.2 +/- 536.3 and 817.9 +/- 494.5-mu-g h l-1, respectively.