Pharmacokinetic studies with chlorthalidone (hygroton^®) in man

Summary

The kinetics of chlorthalidone in blood and urine were analysed in one group of 6 healthy volunteers after single oral doses of 50, 100 and 200 mg, as well as in a second group of 6 volunteers during and after daily oral doses of 50 mg for 14 days. The mean maximal concentrations recorded in blood 8 h after the three different doses were 3.15 µg/ml (SD±0.52), 5.55±1.58 µg/ml and 7.93±1.40 µg/ml, respectively. Disappearance of chlorthalidone from blood followed an apparent first order type of reaction, the average half life t₅₀ being 49 h (SD 11 h). Total renal elimination of unchanged chlorthalidone amounted to 53.3±8.7%, 46.1±8.4% and 34.0±7.3% of the single 50, 100 and 200 mg doses. Between the 6th and 14th days of daily treatment the concentration at the end of the 24 h dose interval was 7.2±1.4 µg/ml (± 1.4) in blood and 186±44 ng/ml in plasma. Except in the early absorption phase after each dose, the distribution of chlorthalidone between erythrocytes and plasma was constant, the average plasma concentration being 1.38±0.28% (n=75) of the whole blood concentration. At steady state during daily dosing with chlorthalidone 50 mg, the renal elimination of unchanged chlorthalidone within each 24 h dose interval was 57±11.2% of the daily dose. The renal plasma clearance ranged from 46 to 70 ml/min. Following termination of repeated administration the concentration of chlorthalidone in blood decreased with a t₅₀=50±5 h and in plasma with t₅₀=49±4.8 h.