ORUDIS SR Capsule Ref.[50303] Active ingredients: Ketoprofen

Ketoprofen is readily absorbed from the gastrointestinal tract, peak plasma concentration occur 0.5 to 2 hours after a single dose. Some retardation in absorption occurs with food. The plasma half-life is about 1.6 to 1.9 hours. Binding to serum proteins (to albumin) of about 62 to 93% has been observed.

Major route of metabolism involves glucuronide formation. Traces also of ring hydroxylated derivatives have been detected. Metabolites are not biologically active.

Ketoprofen does not induce hepatic microsomal enzymes.

Excretion of mainly metabolised (up to 55%) ketoprofen after oral administration varies greatly amongst patients, 30 to 90% of the dose being excreted in urine in 24 hours. Apparent faecal excretion of metabolites ranges over 1 to 8% of orally administered dose in 5 day collections.

The absorption and elimination profiles from oral and rectal administration are identical.

The sustained release form of ketoprofen is based upon a multiple pellet system, each pellet acting as an individual delivery system bounded by a pH sensitive dialysing membrane which prevents release of ketoprofen in the stomach. About 100 pellets are needed to deliver each 100 mg of ketoprofen.

Owing to gradual release of ketoprofen, maximum plasma concentrations occur around 6 hours after administration of a single dose of 200 mg of ketoprofen. These are considerably lower (3.5 + 1 microgram/mL) than those after a single dose of 100 mg of conventional ketoprofen (10 microgram/mL). The release characteristics of Orudis SR result in an apparent elimination half-life of 8.4 hours.

There is some evidence that a heavy meal delays the absorption of ketoprofen from the sustained release formulation. However, the bioavailability of the product is unaffected.

Ketoprofen is eliminated by hepatic metabolism as an ester glucuronide conjugate; a minor pathway being aromatic hydroxylation, the resulting inactive metabolites being excreted by the kidney.

Peak plasma concentration of ketoprofen were higher (5 microgram/mL) and occurred later (10.1 hours) in elderly population (mean age 81) than in young healthy subjects (4.2 microgram/mL, 5.6 hours). The apparent elimination half-life was not significantly altered.

In a study using conventional ketoprofen, a decrease in ketoprofen conjugates and reduction in ketoprofen clearance was reported in elderly subjects (mean age 86.3 years).

Accumulation does not occur upon repeated administration of full adult doses of 200 mg/day provided there is no severe impairment of renal or hepatic function.

Severe impairment of renal function may result in impairment of excretion of conjugated ketoprofen and possible consequent regeneration of free ketoprofen from the conjugate.

Ketoprofen is highly protein bound.

Elderly: clearance & unbound fraction

The plasma and renal clearance of ketoprofen is reduced in the elderly (mean age, 73 years) compared to a younger normal population (mean age, 27 years). Hence ketoprofen peak concentration and AUC increase with increasing age. Data from one trial suggest that the increase is greater in women than in men. It has not been determined whether age-related changes in absorption among the elderly contribute to the changes in bioavailability of ketoprofen (see Section 4.4 Special warnings and precautions for use – Use in the elderly).

Genotoxicity

No data available.

Carcinogenicity

No data available.