Parecoxib Sodium

Cyclooxygenase-2 (COX-2), a key enzyme to catalyzes the formation of prostanoids from arachidonic acid, is involved in inflammatory events. Furthermore, the calpain/PARP/NF-κB inflammatory pathway has been implicated in the damage to the neurovascular unit (NVU) following ischemic stroke. This study investigated the effects of parecoxib, a specific COX-2 inhibitor, on calpain, PARP, NF-κB inflammatory signaling, and NVU damage in the rat model of ischemic stroke. Male Sprague-Dawley rats (n = 107) were subjected to 90 min of ischemia, followed by reperfusion. Parecoxib was administered intraperitoneally 5 min post-ischemia, and the activation of calpain, PARP, and NF-κB-inflammatory signaling, and the NVU damage were evaluated 24 h post-ischemia. It was found that parecoxib alleviated neurological deficits, brain swelling and apoptotic cell death, and decreased infarct volumes 24 h post-ischemia. It decreased the levels of calpain 1 and 2, enhanced the levels of calpastatin, and repressed the activities of calpain in penumbra and core. Meanwhile, it reduced the levels of cytosolic PARP and HMGB1, elevated the level of cytosolic IκBα, lowered the levels of nuclear PARP, poly(ADP-ribose) and NF-κB p65, lessened the levels of cytosolic ICAM-1, IL-1β, MMP-2, and MMP-9, and suppressed the MPO activities in penumbra and core. Additionally, it attenuated the NVU and blood-brain barrier damage in penumbra and core. These data demonstrated that parecoxib exerts its protective effects on the NVU by blocking the over-activation of calpain and PARP, as well as by suppressing NF-κB-mediated inflammatory response during ischemic stroke. Moreover, the findings suggest that COX-2 contributes to NVU damage by up-regulating the calpain/PARP/NF-κB inflammatory pathway during brain ischemia.

This study aimed to evaluate the efficacy of intravenous (IV) parecoxib in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinically significant post-ERCP abdominal pain in patients undergoing their first ERCP.

Participants undergoing ERCP with a native papilla were randomly assigned to receive intravenous parecoxib plus standard IV fluid or standard IV fluid alone. Data on patient characteristics, initial serum bilirubin levels, procedural techniques, papilla type, and endoscopic risk factors were collected. The incidence rates of post-ERCP pancreatitis, hyperamylasemia, and post-ERCP abdominal pain were compared between the groups.

A total of 83 and 82 patients were included in the parecoxib and control groups, respectively. There were no significant between-group differences in comorbidities, pre-procedure risks, or baseline laboratory results. The most common diagnosis after ERCP was bile duct stones (62%). The incidence of post-ERCP pancreatitis was 2.4% in the parecoxib group and 11.0% in the control group (p = 0.058). The incidence of post-ERCP abdominal pain was significantly lower in the parecoxib group than in the control group at both 4 h (26.5% vs. 52.4%, p = 0.001) and 24 h (6.0% vs. 20.7%, p = 0.011) after the procedure.

Intravenous parecoxib was effective in reducing post-ERCP abdominal pain and showed a trend toward a lower incidence of post-ERCP pancreatitis (PEP) in both unselected and high-risk patients, without any serious adverse events. Therefore, intravenous parecoxib may represent a viable alternative for PEP prevention in settings where rectal nonsteroidal anti-inflammatory drugs are unavailable.