Prednisolone

The actions of corticosteroids are mediated by the binding of the corticosteroid molecules to receptor molecules located within sensitive cells. Corticosteroid receptors are present in human trabecular meshwork cells and in rabbit iris ciliary body tissue.

Prednisolone, in common with other corticosteroids, will inhibit phospholipase A2 and thus decrease prostaglandin formation.

Prednisolone is a glucocorticoid which has anti-inflammatory activity.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body’s immune responses to diverse stimuli.

The activation and migration of leucocytes will be affected by prednisolone. A 1% solution of prednisolone has been demonstrated to cause a 5.1% reduction in polymorphonuclear leucocyte mobilisation to an inflamed cornea. Corticosteroids will also lyse and destroy lymphocytes. These actions of prednisolone all contribute to its anti-inflammatory effect.

Prednisolone is rapidly and apparently almost completely absorbed after oral administration; it reaches peak plasma concentrations after 1-3 hours. There is however wide inter-subject variation suggesting impaired absorption in some individuals. Plasma half-life is about 3 hours in adults and somewhat less in children. Its initial absorption, but not its overall bioavailability, is affected by food. Prednisolone has a biological half-life lasting several hours, making it suitable for alternate-day administration regimens.

Absorption following intramuscular injection is relatively slow. Systemic absorption occurs slowly after local, intra-articular injection.

Although peak plasma prednisolone levels are somewhat lower after administration of Prednisolone and absorption is delayed, total absorption and bioavailability are the same as after plain prednisolone. Prednisolone shows dose dependent pharmacokinetics, with an increase in dose leading to an increase in volume of distribution and plasma clearance. The degree of plasma protein binding determines the distribution and clearance of free, pharmacologically active drug. Reduced doses are necessary in patients with hypoalbuminaemia.

Prednisolone is metabolised primarily in the liver to a biologically inactive compound. Liver disease prolongs the half-life of prednisolone and, if the patient has hypoalbuminaemia, also increases the proportion of unbound drug and may thereby increase adverse effects.

Prednisolone is excreted in the urine as free and conjugated metabolites, together with small amounts of unchanged prednisolone.

Significant differences in the pharmacokinetics of prednisolone amongst menopausal women have been described. The postmenopausal women had reduced unbound clearance (30%), reduced total clearance and increased half-life of prednisolone.

Ocular use

The oral availability, distribution and excretion of prednisolone is well documented. A figure of 82 ± 13% has been quoted as the oral availability and 1.4 ± 0.3ml/min/kg as the clearance rate. A half life of 2.1-4.0 hours has been calculated.

With regard to ocular pharmacokinetics, prednisolone sodium phosphate is a highly water soluble compound and is almost lipid insoluble. Therefore, theoretically it should not penetrate the intact corneal epithelium. Nevertheless, 30 minutes after instillation of a drop of 1% drug, corneal concentrations of 10µg/g and aqueous levels of 0.5µg/g have been attained. When a 0.5% solution was instilled in rabbit eyes every 15 minutes for an hour, an aqueous concentration of 2.5µg/ml was measured. Considerable variance exists in the intraocular penetration of prednisolone depending on whether the cornea is normal or abraded.

Absorption

It can be seen that only low levels of prednisolone will be absorbed systemically, particularly where the cornea is intact.

Any prednisolone which is absorbed will be highly protein-bound in common with other corticosteroids.

There are no additional non-clinical data.

The use of prednisolone in ophthalmology is well-established. Little specific toxicology work has been reported, however, the breadth of clinical experience confirms its suitability as a topical ophthalmic agent.