[Chronopharmacokinetics of nadolol in patients with arterial hypertension]

The pharmacokinetics of nadolol in blood serum and its excretion in the urine were studied in 6 male patients (aged from 35 to 59 years) with arterial hypertension for 48 h and, respectively, 72 h after a single per os administration of nadolol in a dose of 80 mg in the morning (9.00 a.m.), in daytime (15.00 p.m.) and in the evening (20.00 p.m.). The concentration of nadolol in the blood serum and urine was determined by high performance liquid chromatography with fluorescence detection. Analysis of the obtained data showed maximum blood serum nadolol concentration and the area under the concentration--time curve to be lower (93 ng/ml and 1786 ng h/ml) in the case of evening medication, and the peroral clearance and kinetic distribution volume to be higher (44.8 l/h and 940 l) than after morning medication (188 ng/ml, 2816 ng h/ml, and 28.4 l/h and 650 l, respectively). The corresponding parameters after daytime medication had intermediate values. The half-life period, mean retention time, and time of achievement of maximum blood serum nadolol concentration did not depend on the time of medication and were in the range of 15.2-15.8 h, 21.1-22.0 h, and 2.9-4.0 h, respectively. The pharmacokinetic parameters characterizing nadolol excretion with the urine were independent of the time of its intake. On the basis of the character of the detected circadian changes in the parameters of nadolol pharmacokinetics it is suggested that these changes reflect the circadian variations in the absorption of the drug in the gastrointestinal tract.