Diclofenac potassium tablets are a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of diclofenac potassium tablets, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
Diclofenac is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available (see Table 1). In some fasting volunteers, measurable plasma levels are observed within 10 minutes of dosing with diclofenac potassium tablets. Peak plasma levels are achieved approximately 1 hour in fasting normal volunteers, with a range of 0.33 to 2 hours. Food has no significant effect on the extent of diclofenac absorption. However, there is usually a delay in the onset of absorption and a reduction in peak plasma levels of approximately 30%.
Table 1: Pharmacokinetic Parameters for Diclofenac
| PK Parameter || Normal Healthy Adults (20 to 52 yrs.) |
| || Mean || Coefficient of Variation (%) |
|Absolute Bioavailability (%)[N = 7] ||55 ||40 |
|Tmax (hr) [N = 65] ||1.0 ||76 |
|Oral Clearance (CL/F; mL/min) [N = 61] ||622 ||21 |
|Renal Clearance (% unchanged drug in urine)[N = 7] ||< 1 ||â€” |
|Apparent Volume of Distribution (V/F; L/kg) [N = 61] ||1.3 ||33 |
|Terminal Half-life (hr) [N = 48] ||1.9 ||29 |
The apparent volume of distribution (V/F) of diclofenac potassium is 1.3 L/kg.
Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15 to 105 mcg/mL) achieved with recommended doses.
Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac.
Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. In patients with renal dysfunction, peak concentrations of metabolites 4'-hydroxy- and 5-hydroxy-diclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects. However, diclofenac metabolites undergo further glucuronidation and sulfation followed by biliary excretion.
One diclofenac metabolite 4'-hydroxy-diclofenac has very weak pharmacologic activity.
Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal half-life of unchanged diclofenac is approximately 2 hours.
The pharmacokinetics of diclofenac have not been investigated in pediatric patients.
Pharmacokinetic differences due to race have not been identified.
Hepatic metabolism accounts for almost 100% of diclofenac elimination, so patients with hepatic disease may require reduced doses of diclofenac potassium tablets compared to patients with normal hepatic function.
Diclofenac pharmacokinetics have been investigated in subjects with renal insufficiency. No differences in the pharmacokinetics of diclofenac have been detected in studies of patients with renal impairment. In patients with renal impairment (inulin clearance 60 to 90, 30 to 60, and < 30 mL/min; N = 6 in each group), AUC values and elimination rate were comparable to those in healthy subjects.