Mechanism of Action

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

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

Prednisolone is a synthetic adrenocortical steroid drug with predominantly glucocorticoid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisolone which are due to its glucocorticoid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion.

Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited.

Prednisolone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisolone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.

Pharmacokinetics

Absorption

The maximum serum concentration of Flo-Pred occurs within 1 to 2 hrs following a single dose of oral administration. Food intake prolongs the time to peak concentration, but does not affect the extent of absorption significantly.

Distribution

Prednisolone is reported to be 70-90% protein-bound in the plasma and the volume of distribution is reported as 0.22 - 0.7 L/kg.

Metabolism

Prednisolone is reported to be metabolized mainly in the liver and excreted in the urine as sulfate and glucuronide conjugates.

Excretion

Flo-Pred is eliminated from the plasma with a half-life of 2 to 3 hours.

Oral administration of single dose of 15 mg/5 mL of Flo-Pred, 15 mg/5 mL Prednisolone USP syrup, and 3X 5 mg Prednisolone USP tablets in 24 adult volunteers yielded comparable pharmacokinetic data:

Table 1. Comparison of Mean Pharmacokinetic Parameters (%CV) in Healthy Volunteers Following a Single Dose of 15 mg/5 mL of Flo-Pred, 15 mg/5 mL Prednisolone USP Syrup, and 3X 5 mg Prednisolone USP Tablets

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