Influence of food and fluid volume on chlorothiazide bioavailability: comparison of plasma and urinary excretion methods.

The bioavailability of chlorothiazide from oral tablets was examined under fasting and nonfasting conditions in healthy male volunteers. Bioavailability was determined from urinary excretion data and plasma chlorothiazide concentrations. Two fasting treatments and one nonfasting treatment yielded similar plasma chlorothiazide profiles, characterized by sharply ascending and descending segments until 12-13 hr postdosing, followed by a prolonged period with variable and erratic chlorothiazide levels. A triexponential function that adequately described mean data from each treatment could not be applied to individual plasma curves because of their variable nature. Chlorothiazide absorption was not influenced by different accompanying water volumes in fasted individuals but was doubled when tablets were administered immediately after a standard meal. Urinary excretion of chlorothiazide correlated well with plasma drug concentrations; 48-hr urinary recovery accounted for 24.7% of a 500-mg dose in nonfasted subjects compared to 12.3 and 14.9% in fasted subjects receiving the drug with 20 and 250 ml of water, respectively. Observed relationships between chlorothiazide dosage and absorption efficiency are consistent with previous suggestions that chlorothiazide absorption from the GI tract is saturable and site specific.