Pharmacodynamics

ANSAID Tablets contain flurbiprofen, a nonsteroidal antiinflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of ANSAID, like that of other nonsteroidal antiinflammatory drugs, is not completely understood but may be related to prostaglandin synthetase inhibition.

Pharmacokinetics

Absorption: The mean oral bioavailability of flurbiprofen from ANSAID Tablets 100 mg is 96% relative to an oral solution. Flurbiprofen is rapidly and non-stereoselectively absorbed from ANSAID, with peak plasma concentrations occurring at about 2 hours (see Table 1). Administration of ANSAID with either food or antacids may alter the rate but not the extent of flurbiprofen absorption. Ranitidine has been shown to have no effect on either the rate or extent of flurbiprofen absorption from ANSAID.

Distribution:The apparent volume of distribution (Vz/F) of both R- and S-flurbiprofen is approximately 0.12 L/Kg. Both flurbiprofen enantiomers are more than 99% bound to plasma proteins, primarily albumin. Plasma protein binding is relatively constant for the typical average steady-state concentrations ( ≤ 10 µg/mL) achieved with recommended doses. Flurbiprofen is poorly excreted into human milk. The nursing infant dose is predicted to be approximately 0.1 mg/day in the established milk of a woman taking ANSAID 200 mg/day (see PRECAUTIONS, Nursing Mothers).

Metabolism: Several flurbiprofen metabolites have been identified in human plasma and urine. These metabolites include 4'-hydroxy-flurbiprofen, 3', 4'-dihydroxy-flurbiprofen, 3'-hydroxy- 4'-methoxy-flurbiprofen, their conjugates, and conjugated flurbiprofen. Unlike other arylpropionic acid derivatives (eg, ibuprofen), metabolism of R-flurbiprofen to S-flurbiprofen is minimal. In vitro studies have demonstrated that cytochrome P450 2C9 plays an important role in the metabolism of flurbiprofen to its major metabolite, 4'-hydroxy-flurbiprofen. The 4'-hydroxy-flurbiprofen metabolite showed little antiinflammatory activity in animal models of inflammation. Flurbiprofen does not induce enzymes that alter its metabolism.

The total plasma clearance of unbound flurbiprofen is not stereoselective, and clearance of flurbiprofen is independent of dose when used within the therapeutic range.

Excretion: Following dosing with ANSAID, less than 3% of flurbiprofen is excreted unchanged in the urine, with about 70% of the dose eliminated in the urine as parent drug and metabolites. Because renal elimination is a significant pathway of elimination of flurbiprofen metabolites, dosing adjustment in patients with moderate or severe renal dysfunction may be necessary to avoid accumulation of flurbiprofen metabolites. The mean terminal disposition half-lives (t 1/2) of R- and S-flurbiprofen are similar, about 4.7 and 5.7 hours, respectively. There is little accumulation of flurbiprofen following multiple doses of ANSAID.

Table 1. Mean (SD) R,S-Flurbiprofen Pharmacokinetic Parameters Normalized to a 100 mg Dose of ANSAID

Special Populations

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