Effects of magnesium oxide on trichlormethiazide bioavailability

The effect of an antacid, magnesium oxide (MgO), on the bioavailability of a thiazide diuretic, trichlormethiazide, was studied in 10 healthy subjects who fasted overnight. A single oral dose of 4 mg of 1 alone or in combination with 0.5 g of MgO was given in a two-way Latin-square crossover design. Urine concentrations of 1 during the 24 h after each dose were determined by an HPLC method. There were no significant differences for drug alone versus drug with MgO in the mean percentage recovery (60 versus 62%) and the cumulative amount excreted unchanged in urine over 24 h (2408 versus 2463 micrograms). However, coadministration of MgO increased the mean excretion rate of 1 at 0.75 h and 1.5 h (p less than 0.05), the cumulative amount excreted unchanged in urine over 2 h (p less than 0.05), and the absorption rate constant (p less than 0.05). Therefore, the extent of bioavailability was not influenced by MgO, but the rate of absorption was enhanced. The solubility of 1 increased remarkably by changing from pH 1.2 to 8.0 (141 to 1365 micrograms/mL). The dissolution rate of 4 mg of 1 in 500 mL of medium was not affected by an increase in pH. However, a 1.5-fold increase of the dissolution rate in 20 mL of medium was observed by changing from pH 1.2 to 7.3.(ABSTRACT TRUNCATED AT 250 WORDS)