Y-site administration of electrolyte solutions and injectable acetaminophen-A physical compatibility study with combinations frequently used in pediatric intensive care and anesthesia.

AIM: Determination of the physical compatibility of acetaminophen and two different electrolyte solutions (an isotonic, balanced electrolyte solution and a hypotonic, glucose containing electrolyte solution) with drugs frequently used in routine pediatric intensive care. METHODS: Analytical investigations for frequently used combinations without pre-existing data were performed. Visual and microscopic observations according to the European Pharmacopeia as well as pH measurements and ultraviolet visible spectrometry at wavelengths of 350, 410 and 550 nm were conducted to analyze physical compatibility. All measurements were performed immediately after mixing as well as 1, 4, and 24 h after. RESULTS: In total, 42 combinations were analyzed. Visual incompatibilities were found with pantoprazole and diazepam with both electrolyte solutions. For furosemide, a particle formation in mixture with the hypotonic glucose-containing electrolyte solution and a change in pH ≥ 0.5 after 24 h with both electrolyte solutions were observed. Ampicillin, cefuroxime, diazepam, furosemide, linezolid, meropenem, and pantoprazole showed an aberration of the absorbance ≥0.04 (350 nm/410 nm) or ≥0.01 (550 nm) in the photometric measurements with the electrolyte solutions. For acetaminophen, a physical incompatibility was observed with ampicillin, diazepam, furosemide, and pantoprazole. CONCLUSION: Most of the analyzed combinations showed no signs of physical incompatibility and may therefore be administered via the same Y-site. However, diazepam, furosemide, and pantoprazole should not be administered simultaneously with acetaminophen or both electrolyte solutions.

Pharmacological characterization of the biosynthesis of prostanoids and hydroxyeicosatetraenoic acids in human whole blood and platelets by targeted chiral lipidomics analysis.

Platelet 12-lipoxygenase(p-12-LOX) is highly expressed in human platelets, and the development of p-12-LOX inhibitors has the potential to be a novel antithrombotic tool by inhibiting thrombosis without prolonging hemostasis. A chiral liquid chromatography-mass spectrometry(LC-MS/MS) method was used to assess the impact of three commercially available LOX inhibitors[esculetin(6,7-dihydroxycoumarin), ML-355(N-2-benzothiazolyl-4-[[(2-hydroxy-3-methoxyphenyl)methyl]amino]-benzenesulfonamide), CDC(cinnamyl-3,4-dihydroxy-α-cyanocinnamate) and acetylsalicylic acid(ASA; a cyclooxygenase-1 inhibitor) on the generation of prostanoids and HETEs(hydroxyeicosatetraenoic acids) in human whole blood allowed to clot for 1 h at 37 °C(serum), platelet-rich plasma(PRP) stimulated with collagen or TRAP-6(a peptide activating thrombin receptor) and washed platelets. In serum, ML-355 did not affect eicosanoid generation, while CDC caused an incomplete reduction of 12S-HETE levels; esculetin inhibited both 12S-HETE and thromboxane(TX)B2 production; ASA selectively affected TXB2 production. In washed platelets stimulated with thrombin, esculetin, and CDC inhibited both 12S-HETE and TXB2 while ML-355 was almost ineffective. In PRP, ML-355, CDC, and esculetin did not affect platelet aggregation associated with incomplete effects on eicosanoid biosynthesis. ASA alone or in combination with ticagrelor(a P2Y12 blocker) affected platelet aggregation associated with profound inhibition of TXB2 generation. P2Y12 receptor signaling contributed to platelet 12S-HETE biosynthesis in response to primary agonists. In conclusion, ML-355, esculetin, and CDC were not selective inhibitors of p-12-LOX in different cellular systems. They did not affect platelet aggregation induced in PRP by collagen or TRAP-6. The characterization of 12-LOX inhibitors on eicosanoids generated in human whole blood is useful for information on their enzyme selectivity, off-target effects, and the possible influence of plasma components on their pharmacological effects.