Pharmacokinetics of tenidap sodium administered with food or antacid in healthy volunteers.
1. The effects of food and antacid on the pharmacokinetics of tenidap were 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 overnight fast, with food or with 20 ml of the antacid Maalox (aluminum hydroxide 1.8 g and magnesium hydroxide 1.2 g). Plasma samples collected immediately before and up to 96 h after each tenidap dose were assayed for tenidap using a validated h.p.l.c. method. The assay data were used to determine the pharmacokinetic parameters of tenidap in each group. 3. Co-administration of tenidap with food produced a statistically significant delay in the rate of absorption (tmax, 4.4 h) (P < 0.001). There was no statistically significant change in Cmax. However, co-administration with the antacid significantly decreased both the mean rate and extent of absorption of tenidap compared with the fasting state: AUC, 420.93 micrograms ml-1 h (antacid), 476.31 micrograms ml-1 h (fasting) (P = 0.026); Cmax 14.3 micrograms ml-1 (antacid), 18.0 micrograms ml-1 (fasting) (P = 0.001); tmax 4.5 h (antacid), 2.9 h (fasting) (P < 0.001). Neither food nor the antacid had any effect on the elimination of tenidap. These changes in tmax are unlikely to be of any clinical significance owing to the long half-life of tenidap. 4. Treatment was well tolerated. Only two adverse events were reported that were considered by the investigator to be related to tenidap. There were no reports of laboratory or cardiovascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)