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.
Anavekar
S N
SN
University of Melbourne, Department of Medicine, Heidelberg, Victoria, Australia.
Howes
L G
LG
Jarrott
B
B
Syrjanen
M
M
Conway
E L
EL
Louis
W J
WJ
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D003000:Clonidine