Pharmacokinetics of fenclofenac following single and multiple doses

The plasma concentration of the anti-inflammatory drug fenclofenac was investigated in volunteers following single oral doses of 200, 500 and 600 mg, as well as multiple doses of 600mg b.i.d. over five days, using gas chromatography with electron capture detection. The pharmacokinetic parameters derived were independent of dose, and the terminal half-life, t1/2, varied independently of dose between 20 and 38 hours (27.23 +/- 1.8 at 600mg). The apparent volume of distribution (Vd area) had similar values at doses of 200, 500 and 600mg of 15.2 +/- 2.6, 18.2 +/- 1.5 and 14.7 +/- 1.7 litres respectively. These small volumes of distribution indicate that fenclofenac distributes mainly into extracellular space. A mean peak plasma concentration of 63.5 +/- 4.6microgram/ml developed after 3 to4 hours following a single 600mg dose whilst a mean steady state plasma concentration (600mg b.i.d.) of 86.9 +/- 5.7 microgram/ml was achieved within four days, and this decayed with a mean terminal half-life of 25.9 +/- 4.2 hours.