Clonidine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Clonidine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Clonidine stimulates alpha 2 -adrenergic receptors in the brain. Clonidine is not a central nervous system stimulant. The mechanism of action of clonidine in ADHD is not known.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Clonidine stimulates alpha 2 -adrenergic receptors in the brain.
Clonidine is not a central nervous system stimulant.
The mechanism of action of clonidine in ADHD is not known.
12.2 Pharmacodynamics Clonidine is a known antihypertensive agent.
By stimulating alpha 2 -adrenergic receptors in the brain stem, clonidine reduces sympathetic outflow from the central nervous system and decreases peripheral resistance, renal vascular resistance, heart rate, and blood pressure.
12.3 Pharmacokinetics Single-dose Pharmacokinetics in Adults Immediate-release clonidine hydrochloride and clonidine hydrochloride extended-release have different pharmacokinetic characteristics; dose substitution on a milligram for milligram basis will result in differences in exposure.
A comparison across studies suggests that the C max is 50% lower for clonidine hydrochloride extended-release compared to immediate-release clonidine hydrochloride.
Following oral administration of an immediate release formulation, plasma clonidine concentration peaks in approximately 3 to 5 hours and the plasma half-life ranges from 12 to 16 hours.
The half-life increases up to 41 hours in patients with severe impairment of renal function.
Following oral administration about 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hours.
About 50% of the absorbed dose is metabolized in the liver.
Although studies of the effect of renal impairment and studies of clonidine excretion have not been performed with clonidine hydrochloride extended-release, results are likely to be similar to those of the immediate release formulation.
The pharmacokinetic profile of clonidine hydrochloride extended-release administration was evaluated in an open-label, three-period, randomized, crossover study of 15 healthy adult subjects who received three single-dose regimens of clonidine: 0.1 mg of clonidine hydrochloride extended-release under fasted conditions, 0.1 mg of clonidine hydrochloride extended-release following a high fat meal, and 0.1 mg of clonidine immediate-release (Catapres ® ) under fasted conditions.
Treatments were separated by one-week washout periods.
Mean concentration-time data from the 3 treatments are shown in Table 7 and Figure 1.
After administration of clonidine hydrochloride extended-release, maximum clonidine concentrations were approximately 50% of the Catapres maximum concentrations and occurred approximately 5 hours later relative to Catapres.
Similar elimination half-lives were observed and total systemic bioavailability following clonidine hydrochloride extended-release was approximately 89% of that following Catapres.
Food had no effect on plasma concentrations, bioavailability, or elimination half-life.
Table 7 Pharmacokinetic Parameters of Clonidine in Healthy Adult Volunteers CATAPRES-Fasted n=15 Clonidine Hydrochloride Extended-Release-Fed n=15 Clonidine Hydrochloride Extended-Release-Fasted n=14 Parameter Mean SD Mean SD Mean SD C max (pg/mL) 443 59.6 235 34.7 258 33.3 AUC inf (hr*pg/mL) 7313 1812 6505 1728 6729 1650 hT max (hr) 2.07 0.5 6.80 3.61 6.50 1.23 T 1/2 (hr) 12.57 3.11 12.67 3.76 12.65 3.56 Figure 1 Mean Clonidine Concentration-Time Profiles after Single Dose Administration Multiple-dose Pharmacokinetics in Children and Adolescents Plasma clonidine concentrations in children and adolescents (0.1 mg bid and 0.2 mg bid) with ADHD are greater than those of adults with hypertension with children and adolescents receiving higher doses on a mg/kg basis.
Body weight normalized clearance (CL/F) in children and adolescents was higher than CL/F observed in adults with hypertension.
Pharmacokinetics
12.3 Pharmacokinetics Single-dose Pharmacokinetics in Adults Immediate-release clonidine hydrochloride and clonidine hydrochloride extended-release have different pharmacokinetic characteristics; dose substitution on a milligram for milligram basis will result in differences in exposure. A comparison across studies suggests that the C max is 50% lower for clonidine hydrochloride extended-release compared to immediate-release clonidine hydrochloride. Following oral administration of an immediate release formulation, plasma clonidine concentration peaks in approximately 3 to 5 hours and the plasma half-life ranges from 12 to 16 hours. The half-life increases up to 41 hours in patients with severe impairment of renal function. Following oral administration about 40% to 60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hours. About 50% of the absorbed dose is metabolized in the liver. Although studies of the effect of renal impairment and studies of clonidine excretion have not been performed with clonidine hydrochloride extended-release, results are likely to be similar to those of the immediate release formulation. The pharmacokinetic profile of clonidine hydrochloride extended-release administration was evaluated in an open-label, three-period, randomized, crossover study of 15 healthy adult subjects who received three single-dose regimens of clonidine: 0.1 mg of clonidine hydrochloride extended-release under fasted conditions, 0.1 mg of clonidine hydr