Pharmacokinetics of hydrochlorothiazide in fasted and nonfasted subjects: a comparison of plasma level and urinary excretion methods

The bioavailability of hydrochlorothiazide from 50-mg oral tablet doses was examined in healthy male volunteers under fasting and nonfasting conditions. Bioavailability was examined from plasma levels and urinary excretion of unchanged drug. The pharmacokinetics of hydrochlorothiazide in plasma could be described in terms of a triexponential function, and the mean drug half-lives determined from the three exponents were 1.0, 2.2, and 9.0 hr. Changing the accompanying fluid volume has no significant effect on hydrochlorothiazide absorption in fasted subjects. Plasma drug levels were significantly reduced in non-fasted individuals, compared with those in fasted individuals. A similar trend was observed in the urinary excretion of hydrochlorothiazide, but differences between treatments were not significant (p greater than 0.05). Mean 48-hr urinary recovery of hydrochlorothiazide was 70.5% of the dose in nonfasted subjects, and 73.5 and 75.0% of the dose in fasted subjects receiving the drug with 20 and 250 ml of water, respectively. The cumulative urinary excretion of hydrochlorothiazide correlated poorly (r = 0.27) with areas under plasma drug level curves, although the correlation between the means of these values for each of the three treatments was high (r = 0.996).. Close similarity was observed between urinary excretion rates of hydrochlorothiazide and the time course of drug concentrations in plasma.