Carteolol

Carteolol is a non-selective beta-adrenergic blocking agent with associated intrinsic sympathomimetic activity (ISA) and without significant membrane stabilizing activity. It has been shown that beta blocking agents with ISA affect cardiac output, heart rate at rest, peripheral vascular resistance and consequently peripheral circulation less than beta blocking agents without ISA.

Carteolol can be characterised by three pharmacological properties:

• Non-cardioselective beta-blockade;
• Partial agonist potential [moderate intrinsic sympathomimetic activity (ISA)];
• Non-significant membrane stabilising effect (local anaesthetic or quinidine-like).

Carteolol reduces normal and elevated intraocular pressure whether or not accompanied by glaucoma. The exact mechanism of the ocular hypotensive effect of beta-blockers has not been definitely demonstrated. However, it appears that ophthalmic beta-adrenergic blocking agents mainly act by reducing aqueous humor production.

Given topically twice daily in controlled clinical trials, carteolol eye drops effectively reduced IOP in patients with glaucoma or ocular hypertension. No significant effects were noted on corneal sensitivity in healthy subjects or tear secretion or pupil size.

Administration of carteolol to the eyes of animals and healthy individuals has shown that carteolol increases the iris tissue blood velocity in the treated eye of rabbits and may increase tissue blood flow in the human optic nerve head.

Whereas topical nonselective beta-adrenergic blockers decrease serum HDL and worsen the total cholesterol/HDL ratio, beta-blockers with intrinsic sympathomimetic activity appear to have a lesser effect.

Absorption

A single ocular instillation of ¹⁴C-labelled carteolol hydrochloride 2% solution into rabbit eyes demonstrated that carteolol penetrates the cornea quickly. The highest concentration levels were found in the cornea, iris, anterior sclera, ciliary body and conjunctiva 30 to 60 minutes after dosing but declined rapidly to 5 to 10% of the maximum level after 8 hours.

Biotransformation

CYP2D6 mediated 8-hydroxylation is the only cytochrome P450 catalyzed metabolic reaction of carteolol. Carteolol has neither stimulatory nor inhibitory effects on CYP1A2, 2C9, 2C19, 2E1, and 3A4 activities. 8- Hydroxycarteolol was estimated to be more potent than carteolol in lowering IOP both in rabbits and in monkey. No data is available on metabolism after ocular application of carteolol in humans.

Elimination

One drop of a 2% carteolol hydrochloride solution was instilled in each eye of healthy volunteers. Approximately 16% of the dose was excreted in the urine as unchanged compound during the first 24 hours after instillation. The urinary elimination half-life was about 5 hours. The plasma level of carteolol hydrochloride after topical administration in the eye was below the detection limit (5ng/mL).

Preclinical data reveal no special hazard for humans based on conventional studies of acute and repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.