Abstract
1. The kinetics of diclofenac (I) and five of its metabolites (II-VI) were investigated in three healthy volunteers and in six patients. Compounds I-VI were measured by capillary column gas chromatography in plasma and urine.
2. After a single 100mg dose of diclofenac sodium to volunteers, the drug was absorbed rapidly and showed peak plasma levels of 10-12nmol/g. The maximum concentrations of five metabolites were comparatively low (0·36-2·94nmol/g). The mono- and dihydroxy metabolites (II-V) had apparent terminal half-lives similar to that of I (1-3 h), but the hydroxymethoxy metabolite (VI) had a half-life of about 80 h. Renal elimination of VI within 96 h was about 1% of dose and that of I-VI was 36% (free plus conjugated).
3. Following daily treatment with 2×75mg of an experimental sustained release formulation to patients for 6–10 months, steady-state trough concentrations of I-V in plasma were low (average values: 0·23-0·57 nmol/g). The mean trough concentration of VI was comparatively higher at 3·69·0·91 nmol/g presumably reflecting its accumulation. Despite this it is unlikely to contribute to the drug' therapeutic activity, since it has been shown in laboratory tests to be devoid of anti-inflammatory activity.