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Phospholipase-A2 has been suggested as having a role in the pathophysiology of acute pancreatitis. The inhibition of phospholipase-A2 was studied in vitro using 17 pharmacological agents in the search for a specific therapy for acute pancreatitis. The inhibitory effect was tested using an isotopic assay system with 2-palmitoyl-(1-14C)-labelled dipalmitoyl phosphatidylcholine as a substrate and 10 microliters of serum from patients with acute necrotizing pancreatitis as an enzyme source. Among all agents tested, anti-inflammatory drugs inhibited enzyme activity most significantly: indomethacin (9.0 x 10(-3) mol l-1) decreased the phospholipase-A2 activity to one- tenth. The weak inhibitory effect could also be demonstrated using a lower concentration of 2 x 10(-5) mol l-1, which can be achieved after intravenous administration of 50 mg of this drug. The other drugs inhibited the enzyme activity at concentrations higher than those achieved after intravenous injections in clinical use. Diclofenac (3.1 x 10(-2) mol l-1) reduced the phospholipase-A2 activity by 93%, ketoprofen (2.0 x 10(-2) mol l-1) or chlorpromazine (1.4 x 10(-2) mol l-1) by 90%, tobramycin (1.7 x 10(-2) mol l-1) by 84%, doxycycline (9.0 x 10(-3) mol l-1) by 61%, dexamethasone (1.7 x 10(-3) mol l-1) by 62%, methylprednisolone (3.8 x 10(-2) mol l-1) by 50%, and pindolol (1.0 x 10(-4) mol l-1) by 59%. A weak inhibition of phospholipase-A2 activity was demonstrated by betamethasone, bupivacaine, digoxin, hydrocortisone, lidocaine, metoprolol, propranolol, and vancomycin. Indomethacin proved the most potent of the tested agents in inhibiting phospholipase-A2 activity in serum from patients with acute pancreatitis and should be further studied in vivo.
Mäkelä et al. (Wed,) studied this question.