The effect of dosage on the bioavailability of chlorothiazide administered in solution

Chlorothiazide in solution was administered at four dose levels to three healthy male volunteers under controlled conditions. Excretion data indicated that the drug was poorly absorbed from the gastrointestinal tract. The 24 h recovery of the drug from urine fell from 33 to 6% as the dose was increased from 0.21 to 1.75 g per 70 kg of body weight. The cumulative amount of sodium excreted could be correlated with the cumulative amount of drug excreted, rather than with the dose administered. The electrolyte excretion response intensity could also be correlated with the amount of drug excreted. There was a poor linear relationship between response intensity and drug excretion rate. After higher doses the data suggested that the response was in the non-linear section of the dose response curve.