Large differences in the biological half-life and volume of distribution of hydrochlorothiazide in normal subjects from eleven studies. Correlation with their last blood sampling times.

In spite of more than three decades of wide use of hydrochlorothiazide as a diuretic, its mean biological half-life (t1/2) and apparent volume of distribution (Vdarea) in normal subjects were found to vary greatly among 11 studies reported between 1976 and 1986. For example, the mean t1/2 values ranged from 3.2 to 13.1 h and Vdarea values from 1.53 to 4.19 l/kg. Furthermore, a t1/2 of only 2.5 h and a Vdarea of only 0.83 l/kg were cited in a recent textbook. The present analyses show a positive correlation between the length of the last blood sampling time (tlast) employed and the t1/2 or Vdarea. The smaller t1/2 and Vdarea values reported were attributed to the insufficient length of time used in blood sampling for a drug exhibiting polyexponential disposition function. The kinetic and dynamic significance of the findings were briefly described.