Clonidine pharmacokinetics

CH Chiang, RD Schoenwald. (1986). Ocular pharmacokinetic models of clonidine-3H hydrochloride. J Pharmacokin Biopharm 14 175-211. 

Pharmacology Initially, clonidine stimulates peripheral -adrenergic receptors producing transient vasoconstriction. Stimulation of alpha-adrenergic in the brain stem results in reduced sympathetic outflow from the CNS and a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Pharmacokinetics Blood pressure declines within 30 to 60 minutes after an oral... 

Clonidine is one of the most widely used sedating medications in pediatric and child psychiatry practice, particularly in children with sleep onset delay and ADHD. It is a central alpha2 agonist. Pharmacokinetics show rapid absorption, with an onset action within 1 h, peak effects at 2-4 h and a half-life 6-24 h. Effects on sleep architecture are fairly minimal but may include decreased REM, so that discontinuation can lead to REM rebound. Clonidine has a narrow therapeutic index, and there has been a recent dramatic increase in reports of overdose with this medication. Potentially significant side effects including hypotension, bradycardia, anticholinergic effects, irritability, and dysphoria rebound hypertension may occur on abrupt discontinuation. Tolerance often develops, necessitating increases in dose. 

Clonidine (CL) Male (18-45) Chest, arm Catapres-TTS patch CL concentration in plasma Similar pharmacokinetic profile between sites ... 

Clonidine (CL) Male (26-41) Right chest, left arm, upper abdomen Patch Pharmacokinetic parameters Plasma concentration of CL, Cmax- AUC Left arm were greater than right chest and abdomen. Blood pressure lowering arm > abdomen. V... 

Shaw, J.E. (1984) Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route. American Heart Journal, 108, 217-222. 

Fujimura A, Ebihara A, Ohashi K-l, et al. Comparison of the pharmacokinetics, pharmacodynamics, and safety of oral (Catapres) and transdermal (M-5041T) clonidine in healthy subjects. J Clin Pharmacol 1994 34 260-265. 

E. Pharmacokinetics. The onset of effects is rapid (30 min) after oral administration of clonidine. Other than methyidopa, the dmgs are widely distributed with large volumes of distribution (see also Table 11-59). 

Its duration of action is 60-120 minutes, depending on the vascularity of the site blocked as well as added adjuvants such as epinephrine. The drug is 70% protein-bound, with 30% in the free unbound form. It is this 30% that is rapidly cleared by the systemic circulation for hepatic metabolism. The vasoconstrictive properties of epinephrine help to decrease this systemic uptake of the drug and thus to prolong its duration of action. Other adjuvants such as the alpha-2 receptor agonists clonidine and dexmedetomidine have been studied recently and found to prolong the duration of action of lidocaine. Their mechanism of action (specific receptor vs. pharmacokinetic/phar-macodynamic interaction with local anesthetics) and site (central vs. peripheral) of action have not been fully elucidated [6-8]. 

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