Pharmacokinetics and antihypertensive effects of low dose clonidine during chronic therapy.

Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml were achieved after 3.6 +/- 1.2 hours. After 5 days of repetitive dosing the maximal concentration was significantly higher, 0.66 +/- 0.06 ng/ml and remained so throughout chronic therapy (P = 0.018). The AUC, Tmax and T1/2 did not differ significantly between the acute dose and the chronic dosing pharmacokinetic studies. Clonidine also produced a significant fall in blood pressure. Supine diastolic blood pressure fell from 106 +/- 5 mmHg predose to 99 +/- 6 mmHg 2 hours after the first dose (P less than 0.05). The corresponding values after cyclopenthiazide alone were 108 +/- 8 and 105 +/- 8 mmHg (P = 0.13). Similar falls in blood pressure were produced during chronic therapy.