Animal experiment:

Rats[1]After 2 weeks of acclimatization, rats are randomized to different groups and given the non-selective COX inhibitors, amtolmetin guacyl (AMG) (50 and 150 mg/kg) and Tolmetin (30 and 100 mg/kg) as well as the selective COX-2 inhibitor, celecoxib (CXIB; 20 and 60 mg/kg). The compounds are suspended in 1% carboxymethylcellulose (CMC) immediately before use and administered by gavage in a 10-mL/kg volume. Control groups receive CMC in the same volume. Rats from each group are divided into 3 subgroups, consisting each of at least 10 animals. Subgroups are dosed either with a single dose (acute treatment group) or twice daily for 3 and 14 days (chronic treatment groups). To ensure that all groups are dosed for the same period of time, those receiving less than 14 days of NSAIDs are given CMC until they are due to start the assigned treatment. Rats are killed by cervical dislocation 4 h after the last administration. Stomachs are immediately removed, opened along the lesser curvature and gently rinsed[1].

Tolmetin is a non-steroidal anti-inflammatory drug that non-selectively inhibits human COX-1 and -2 [1].

The cyclooxygenase (COX) is a therapeutic target for preventing cancer. Two isoforms of COX have been identified: COX 1 and COX 2. COX 1 has been constitutively expressed in most tissues and involved in mediating production of prostaglandins that control normal physiological functions, such as maintenance of the gastric mucosa and regulation of renal blood flow. COX 2 is undetectable in most normal tissues [2].

In vitro: Tolmetin inhibited the activity of human COX-1 and -2 with IC50 values of 0.35 and 0.82 μM, respectively [1]. Tolmetin was a competitive and reversible inhibitor of prostaglandin synthetase [3].

In vivo: In rats, pretreatment with tolmetin reduced prostaglandin synthesis by minces of renal medulla. Incubation of medullary tissue with tolmetin decreased prostagland production. In anesthetized dogs, Tolmetin reduced renal blood flow and shifted the distribution of renal cortical flow from the inner cortex toward the outer cortex [4].

References:
[1] Warner T D, Giuliano F, Vojnovic I, et al.  Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis[J]. Proceedings of the National Academy of Sciences, 1999, 96(13): 7563-7568.
[2] Dannenberg A J, Altorki N K, Boyle J O, et al.  Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer[J]. The lancet oncology, 2001, 2(9): 544-551.
[3] Taylor R J, Salata J J.  Inhibition of prostaglandin synthetase by tolmetin (Tolectin, McN-2559), a new non-steroidal anti-inflammatory agent[J]. Biochemical pharmacology, 1976, 25(22): 2479-2484.
[4] Noordewier B, Stygles V G, Hook J B, et al.  Effect of tolmetin on renal function and prostaglandin metabolism[J]. Journal of Pharmacology and Experimental Therapeutics, 1978, 204(2): 461-468.