Table 1.
Representative studies on the effect of Ibuprofen in platelets.
| NSAID Drug (s) | Study Design | Effects on Platelets | Ref |
|---|---|---|---|
| AA and Ibuprofen in blood samples from humans and pigs | Iv vitro In blood samples from 4 pigs. Dose: different dosages (from 1 to 20) of 163 mg/mL ibuprofen were added and platelet aggression was examined 15 min later. In vitro. Blood samples from 6 healthy individuals and 6 pigs. Dose: different dosages (from 1 to 20) of 163 mg/mL ibuprofen were added. Platelet aggression was examined 15 min later. |
Ibuprofen inhibited AA-/collagen-induced platelet aggregation, with higher sensitivity in human blood samples in blood samples of both human and pigs (collagen induced platelet aggression was degreased to 10% ± 5% for 20 dosages of ibuprofen at pig blood samples) PT and clot formation time remained unchanged by ibuprofen at recommended (x1) doses, while coagulation was compromised at higher ibuprofen doses (x16), as aPTT exhibited a notable extension |
[58,70] |
| ASP6537, aspirin, clopidogrel and Ibuprofen in a FeCl3-induced thrombosis model in guinea pigs | In vivo (Animal model). Guinea pigs were divided into 6 groups. Dose: orally administrated 30 mg/kg Ibuprofen 1 h before been administrated 30 mg/kg ASP6537 or 100 mg/kg aspirin. |
Prior administration of ibuprofen nullified the suppressive impact of aspirin on collagen-induced platelet aggregation Ibuprofen was not able to affect the inhibitory activity of ASP6537 |
[60] |
| Paracetamol and ibuprofen in patients who underwent neurovascular stent placement and subsequently underwent VPS surgery while on dual antiplatelet therapy | In vivo study (Clinical Trial). Participants were 41 patients who were administrated dual antiplatelet therapy and they were divided into 2 groups. Dose: 0.6 g ibuprofen twice a day First group temporarily halted dual antiplatelet therapy (DAPT) for a five-day duration ibuprofen administration while second group continued their DAPT therapy. |
Hemorrhagic complications were significantly more prevalent in the group that the dual antiplatelet therapy was maintained during surgery, in contrast to the group that adopted ibuprofen bridging therapy. No observed ischemic complications in patients of both groups |
[63] |
| Aspirin, Ibuprofen in vitro in hPRP or hWP from blood samples of human healthy volunteers | In vitro study. Blood samples were taken from healthy individuals who stopped taking pharmaceuticals compounds 14 days prior. Platelet rich plasma (hPRP) was mixed with 80 μM ibuprofen, aspirin or salicylic acid for 30 min and 23 °C. |
Ibuprohfen inhibited the ADP-induced secondary phase of platelet aggregation (from 21.3 ± 5.6 pmol/mL to 14.8 ± 3.4 pmol/mL). Ibuprofen also stimulated the production of NO, a potent inhibitor of platelet aggregation, in the absence of added ADP in both hPRP and hWP. The latent indicates that this effect was not mediated through plasma proteins. Either a temporary or a lasting inhibition of prostaglandin synthesis by ibuprofen resulted in the synthesis of NO in resting platelets. |
[56] |
| acetylsalicylic acid, dexibuprofen, ibuprofen, or flurbiprofen in whole blood samples of healthy donors | In vitro. Blood samples were from volunteers without medication for 2 weeks. Dose: 0.01 to 100 μΜ of acetylsalicylic acid, dexibuprofen, ibuprofen, or flurbiprofen. |
Ibuprofen inhibited ADP-/AA-/Collagen-induced platelet aggregation in a dose-dependent manner (IC50 (μΜ): ADP: 36.1 ± 2.4, Collagen: 29.8 ± 1.1, AA: 14.7 ± 1.2) Inhibition of the platelet synthesis of both TxB2 (IC50 101 ± 9.46) and LPS-induced PGE2 (IC50 39.33 ± 2.14), as well as the leukocyte production of both PGF1α (IC50 96.32 ± 4.90) and calcium-induced NO (8.55 ± 0.09) synthesis were observed due to incubation of each cells with increasing concentrations of ibuprofen, and increased nitric oxide production |
[57] |
| Different cyclooxygenase (COX) inhibitors, including ibuprofen against platelet aggregation in human blood samples | In vitro. Blood samples were retrieved from healthy individuals who have not taken any medication for 7 days). 45 mL of platelet reach plasma was diluted to 0.5 mL by adding the pharmaceutical compound. |
Recommended concentrations of Ibuprofen inhibited the enhanced aggregation of platelets by the co-induction from two different platelet agonists, AA with either 5-HT or ADP (IC50: 18.0 ± 1.8). | [59] |
| Ibuprofen-arginine (an Ibuprofen arginate derivative) | In vitro study. Participants gave blood samples. |
The ibuprofen derivative showed improved inhibition of AA-induced platelet aggregation in platelet-rich plasma of healthy donors and colon cancer cell killing in human epithelial colorectal adenocarcinoma cell line, Caco-2 | [13] |
| Ibuprofen derivative | In vitro study. Participants were healthy individuals from whom blood samples were taken. Dose: from 0 to 100 μΜ of every ibuprofen derivative |
Antioxidant properties The ibuprofen derivative with the highest antioxidant properties was also able to dose dependently mitigate the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets, as assessed by various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins The same most antioxidant ibuprofen-derivative compound dose dependently ameliorated platelet aggregation induced by ADP, Collagen and epinephrine |
[68] |
| Ibuprofen | In vitro study. Platelets from Sprague–Dawley rats. Dose: 0.3 μΜ ibuprofen. NGF and BDNF were analyzed after 10 and 6-min. |
incubation of Sprague-Dawley rat platelets with ibuprofen showed that the spontaneous release from platelets of both NGF and BDNF (10–15%) neural growth factors, implicated in neurodegenerative disorders, were differentially influenced (reduced), in a time-, dose- and calcium-specific pattern, suggesting neuroprotective properties for ibuprofen | [69] |
Abbreviations: NSAID(s) = non-steroidal anti-inflammatory drug(s); AA = arachidonic acid; ADP = adenosine 5′ diphosphate; PT = prothrombin time; aPTT = activated partial thromboplastin time; ASP6537 = a selective cyclooxygenase-1 (COX-1) inhibitor; hPRP = human platelet-rich plasma; hWP = human-washed platelets; NO = nitric oxide; TxB2 = thromboxane B2; LPS = bacterial membrane lipopolysaccharide; PGE2 = prostaglandin E2; PGF1α = 6-keto-prostaglandin F1α; 5-HT = 5-hydroxytryptamine; ROS = reactive oxygen species; PS = phosphatidylserine; LDH = lactate dehydrogenase; NGF = nerve growth factor; BDNF = brain-derived neurotrophic factor.