Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine.
The kinetics of the disposition of intravenous and oral clonidine in five normotensive subjects have been determined. It is proposed that a two-compartment model adequately describes the disposition of the drug. The drug is rapidly distributed (t1/2alpha = 10.8 +/- 4.7 min) but slowly elimainated (t1/2beta = 8.5 +/- 0.9 hr). The bioavailability of oral clonidine in the tablets tested averaged 75.2% and 40 to 50% of the bioavailable dose is excreted unchanged in urine. Renal clearance of the drug showed considerable intersubject variation (1.82 +/- 0.34 ml/min/kg) and exceed the calculated glomerular filtration rate in some subjects. Oral and intravenous clonidine induced significant falls in blood pressure (greater than 20/15 mm Hg) in our normotensive subjects and consistently caused marked sedation and dryness of the mouth. Sedation and salivary flow correlated with plasma clonidine concentration over the range 0 to 4 ng/ml. Falls in blood pressure were related to plasma concentration to 1.5 to 2 ng/ml but at higher concentrations the hypotensive effect was attenuated.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D003201:Computers; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D012472:Salivation / Q000187:drug effects; D014987:Xerostomia / Q000139:chemically induced
D006993:Hypnotics and Sedatives; D003000:Clonidine