A novel method for the simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in biological fluids by gas liquid chromatography is described. The assay has been used to determine the plasma concentration of salicylates in 10 volunteers after oral ingestion of three commercially available aspirin-containing formulations. No difficulty was encountered in determining low concentrations of acetylsalicylic acid in the presence of higher concentrations of salicylic acid. The in vivo plasma half life of acetylsalicylic acid in man was found to be 15.5 min.
1. The excretion and metabolism of radiolabelled fenclofenac (2-(2,4-dichlorophenoxy)phenylacetic acid, Flenac) has been studied in five species. 2. In the rat, absorption of oral doses of fenclofenac was virtually complete and elimination occurred mainly by the bile and faeces. The guinea-pig excreted equal amounts of radioactivity in urine and faeces, while in rabbit, baboon and man renal excretion was the more important route. 3. In all species the majority of excreted radioactivity was present as fenclofenac ester glucuronide. Amino acid conjunction with fenclofenac was minimal in all species studied. 4. Mono- and di-hydroxylated metabolites have been detected in urine from guinea-pig, baboon and man. The major hydroxylated metabolite in baboon urine has been identified as 2-(2,4-dichlorophenoxy)-5'-hydroxyphenylacetic acid.
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.
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