PHARMACOKINETICS OF TENIDAP SODIUM ADMINISTERED WITH FOOD OR ANTACID IN HEALTHY-VOLUNTEERS

1 The effects of food and antacid on the pharmacokinetics of tenidap w ere investigated in this randomised, 3-way cross-over study. 2 Twenty- one healthy young men, mean age 27.4 years, received single oral doses of tenidap sodium 120 mg at weekly intervals after either an overnigh t fast, with food or with 20 mi of the antacid Maalox(R) (aluminium hy droxide 1.8 g and magnesium hydroxide 1.2 g). Plasma samples collected immediately before and up to 96 h after each tenidap dose were assaye d for tenidap using a validated h.p.l.c. method. The assay data were u sed to determine the pharmacokinetic parameters of tenidap in each gro up. 3 Co-administration of tenidap with food produced a statistically significant delay in the rate of absorption (t(max), 4.4 h) (P < 0.001 ). There was no statistically significant change in C-max. However, co -administration with the antacid significantly decreased both the mean rate and extent of absorption of tenidap compared with the fasting st ate: AUG, 420.93 mu g ml(-1) h (antacid), 476.31 mu g ml(-1) h (fastin g) (P = 0.026); C-max 14.3 mu g ml(-1) (antacid), 18.0 mu g ml(-1) (fa sting) (P = 0.001); t(max) 4.5 h (antacid), 2.9 h (fasting) (P < 0.001 ). Neither food nor the antacid had any effect on the elimination of t enidap. These changes in t,,, are unlikely to be of any clinical signi ficance owing to the long half-life of tenidap. 4 Treatment was well t olerated. Only two adverse events were reported that were considered b y the investigator to be related to tenidap. There were no reports of laboratory or cardiovascular abnormalities. 5 The reduced rate of abso rption with food is probably a consequence of delayed stomach emptying , whereas the reduced extent of absorption with antacid (11%) probably results from adsorption. These reductions are unlikely to be of clini cal significance.