Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties

Pharmacotherapeutic Group: Throat preparations, other throat preparations.

ATC Code: R02AX01

Flurbiprofen is a propionic acid derivative NSAID which acts through inhibition of prostaglandin synthesis. In humans flurbiprofen has potent analgesic, antipyretic and anti-inflammatory properties and the 8.75mg dose dissolved in artificial saliva has been shown to reduce prostaglandin synthesis in cultured human respiratory cells.
According to studies using the whole blood assay, flurbiprofen is a mixed COX- 1/COX-2 inhibitor with some selectivity towards COX-1.
Pre-clinical studies suggest that the R (-) enantiomer of flurbiprofen and related NSAIDs may act on the central nervous system; the suggested mechanism is by inhibition of induced COX-2 at the level of the spinal cord.
A single dose of flurbiprofen 8.75mg delivered locally to the throat in a lozenge has been demonstrated to relieve sore throat, including swollen and inflamed sore throats through a significant reduction (LS Mean Difference) in sore throat pain intensity from 22 minutes (-5.5mm), reaching a maximum at 70 minutes (-13.7mm) and remaining significant for up to 240 minutes (-3.5mm) including patients with streptococcal and non-streptococcal infections, reduction in difficulty swallowing from 20 minutes (-6.7mm), reaching a maximum at 110 minutes (-13.9mm) and for up to 240 minutes (-3.5mm) and reduction in the feeling of a swollen throat at 60 minutes (-9.9mm), reaching a maximum at 120 minutes (-11.4mm) and for up to 210 minutes (-5.1mm).
Multiple dose efficacy measured using Sum of Pain Intensity Differences (SPID) over 24 hours has demonstrated significant reduction in sore throat pain intensity (-
473.7mm*h to -529.1mm*h), difficulty swallowing (-458.4mm*h to -575.0mm*h) and swollen throat (-482.4mm*h to -549.9mm*h) with statistically significant greater summed reduction in pain at each hourly interval over 23 hours for all three measures and statistically significantly greater sore throat relief each hour over the 6 hour assessment time. Efficacy of multiple doses after 24 hours and over 3 days has also been demonstrated.
For those patients taking antibiotics for streptococcal infection, there was statistically significant greater relief of sore throat pain intensity for flurbiprofen 8.75mg from 7 hours and onwards after antibiotics were taken. The analgesic effect of flurbiprofen 8.75 mg was not reduced by the administration of antibiotics to treat patients with streptococcal sore throat.
At 2 hours post first dose, flurbiprofen 8.75mg lozenges provided significant resolution of some of the associated symptoms of sore throat present at baseline including coughing (50% vs 4%), loss of appetite (84% vs 57%) and feverishness (68% vs 29%). The lozenge format dissolves in the mouth over 5 - 12 minutes and provides a measurable soothing and coating effect at 2 minutes.

Paediatric Population
No specific studies in children have been undertaken. Efficacy and safety studies on flurbiprofen 8.75mg lozenges have included children aged 12 – 17 years, although small sample size means that no statistical conclusions can be drawn.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties

Absorption
Flurbiprofen 8.75mg lozenges dissolve over 5 – 12 minutes and the flurbiprofen is readily absorbed, with detection in the blood at 5 minutes and plasma concentrations peaking at 40 - 45 minutes after administration but remaining at a mean low level of 1.4µg/mL which is approximately 4.4 times lower than a 50mg tablet dose.
Absorption of flurbiprofen can occur from the buccal cavity by passive diffusion. Rate of absorption is dependent on pharmaceutical form with peak concentrations achieved more rapidly than, but of similar magnitude to, those achieved after an equivalent swallowed dose.

Distribution
Flurbiprofen is rapidly distributed throughout the body and is extensively bound to plasma proteins.

Metabolism / Excretion
Flurbiprofen is mainly metabolised by hydroxylation and excreted via the kidneys. It has an elimination half-life of 3 to 6 hours. Flurbiprofen is excreted in very small amounts in human milk (less than 0.05 µg/ml). Approximately 20-25% of a flurbiprofen oral dose is excreted unchanged.

Special Groups

No difference in pharmacokinetic parameters between elderly and young adult volunteers has been reported following oral administration of flurbiprofen tablets. No pharmacokinetic data have been generated in children below 12 years of age following administration of Flurbiprofen 8.75 mg, however administration of both flurbiprofen syrup and suppository formulations indicate no significant differences in pharmacokinetic parameters compared with adults.