[The pharmacokinetic behavior of AWD 26-06 in humans following single and multiple administration]

The pharmacokinetics of the muscarinolytic drug AWD 26-06 was investigated in two subjects after a single dose of 50 and 100 mg, respectively, and with six subjects after repeated dosage. The half time (t1/2) is 2.4 and 2.6 h, respectively, the height of the concentration maximum (Cmax) 500 and 1400 ng.ml-1, respectively, and the area under the curve (AUC) 2155 and 4334 ng.ml-1.h, respectively. The repeated dosage (25 mg every 8 h for 7 d) showed a small increase of the serum level. The t1/2 and the mean residence time (MRT) at the 1st and the 8th d are 2.6 h (range: 1.8-2.9 h) and 4 h (range: 2.7-5.8 h), respectively. The point (tmax) and the Cmax were not different at the 1st and 8th d: mean tmax (1st d) 1.1 h (range: 1.0-1.5 h), mean tmax (8th d) 0.9 h (range: 0.75-1.0 h); Cmax (1st d) 227 ng.ml-1 (range: 160-320 ng.ml-1), Cmax (8th d) 282 ng.ml-1 (range: 168-320 ng.ml-1). There were also no differences for the AUC0-t at the 1st and 8th d (1st d) 815 ng.ml-1.h (range: 610-1134 ng.ml-1.h). The simulation of the serum level by means of the data from the single dose were established by this investigation. Typical subjective muscarinolytic symptoms (e.g. dryness of the mouth, diminution of accommodation) were observed after the 2nd/3rd dosage. These signs diminished 24-36 h after discontinuation of the dosage. The parameter ALAT, proteins of plasma, and blood cell count were not changed at the end of therapy in comparison to the beginning.