Details

Autor(en) / Beteiligte

• Senarathna, S.M.D.K. Ganga
• Strunk, Tobias
• Petrovski, Michael
• Woodland, Sarah
• Batty, Kevin T.

Titel

Physicochemical compatibility of pentoxifylline injection with high‐concentration parenteral medications

Ist Teil von

• Pediatric investigation, 2023-12, Vol.7 (4), p.263-267

Ort / Verlag

Hoboken: John Wiley & Sons, Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• An established procedure, including a validated, stability-indicating high-performance liquid chromatography (HPLC) assay was used for evaluating the physical and chemical compatibility of the PTX-drug combinations at room temperature. 3,4,6 Briefly, clear glass vials with impermeable lids were used for each combination of drugs and the respective control solutions: PTX solution and the test drug solution were combined 1:1 in each of the four vials; PTX solution was diluted 1:1 with 0.9% w/v sodium chloride injection (n = 4 vials) as the reference solution for the purposes of visual comparison and HPLC assay, and; The test drug solution was diluted 1:1 with the applicable diluent (n = 4 vials) for the purpose of visual comparison. TABLE 1 Ratio of pentoxifylline (PTX) concentration when combined with the test drug, compared to PTX standard solution (2.5 mg/ml) Drug Test concentration Diluent PTX ratio (%) 95% CI of the ratio Acyclovir (mg/ml) 5 D5W 99.5 98.9‒100.1 Alprostadil (µg/ml) † 10 NS 99.9 99.4‒100.5 Alprostadil (µg/ml) † 20 NS 99.9 99.5‒100.3 Amoxicillin (mg/ml) 100 WfI 95.8 95.0‒96.6 Ampicillin (mg/ml) 100 WfI 96.9 95.6‒98.2 Calcium gluconate (mg/ml) †‡ 100 U 99.7 99.3‒100.0 Cloxacillin (mg/ml) 100 WfI 100.1 99.1‒101.1 Dopamine (mg/ml) 1.6 NS 97.6 95.9‒99.2 Dopamine (mg/ml) 1.6 D5W 99.3 98.7‒100.7 Dopamine (mg/ml) † 7.2 NS 99.2 98.7‒99.7 Dopamine (mg/ml) † 7 D5W 99.2 99.0‒99.4 Epinephrine (µg/ml) † 25 D5W 99.8 99.1‒100.4 Epinephrine (µg/ml) † 50 D5W 99.5 98.8‒100.1 Fentanyl (µg/ml) 5 D5W 100.0 98.7‒101.3 Fentanyl (µg/ml) 25 D5W 99.2 97.4‒101.0 Fentanyl (µg/ml) 50 U 100.1 99.6‒100.6 Fluconazole (mg/ml) ‡ 2 NS 99.4 98.8‒100.1 Furosemide (mg/ml) † 1 NS 100.0 99.7‒100.3 Furosemide (mg/ml) † 1 D5W 99.6 99.2‒100.0 Hydrocortisone (mg/ml) 2 NS 99.2 97.9‒100.5 Ibuprofen lysine (mg/ml) 4 NS 99.3 98.9‒99.8 Ibuprofen lysine (mg/ml) 4 D5W 100.4 99.1‒101.8 Midazolam (µg/ml) 120 D5W 99.4 98.6‒100.2 Midazolam (µg/ml) 120 D10 99.1 98.0‒100.2 Midazolam (µg/ml) 500 D5W 99.8 99.5‒100.1 Midazolam (µg/ml) ‡ 500 D10 99.7 99.5‒99.9 Midazolam (mg/ml) † 1 U 99.7 99.4‒100.1 Midazolam (mg/ml) †§ 1 NS 99.0 97.5‒100.5 Midazolam (mg/ml) †§ 1 D5W 99.8 99.3‒100.4 Milrinone (µg/ml) 200 NS 99.3 98.5‒100.1 Milrinone (µg/ml) 200 D5W 100.0 99.0‒101.0 Milrinone (µg/ml) † 400 NS 100.2 99.2‒101.3 Milrinone (µg/ml) †‡ 400 D5W 100.1 99.7‒100.5 Morphine hydrochloride (µg/ml) 200 NS 99.2 98.8‒99.7 Morphine hydrochloride (µg/ml) 200 D10 97.9 97.2‒98.5 Morphine hydrochloride (µg/ml) † 500 NS 99.9 99.2‒100.6 Morphine hydrochloride (µg/ml) † 500 D5W 99.4 98.8‒100.0 Morphine hydrochloride (µg/ml) † 500 D10 100.3 99.8‒100.7 Morphine sulfate (µg/ml) 200 NS 98.3 97.1‒99.6 Morphine sulfate (µg/ml) ‡ 200 D10 100.4 99.8‒101.0 Morphine sulfate (µg/ml) † 500 NS 100.3 100.0‒100.5 Morphine sulfate (µg/ml) † 500 D5W 100.2 99.8‒100.6 Morphine sulfate (µg/ml) † 500 D10 100.9 99.7‒102.1 Norepinephrine (µg/ml) ‡ 12 D5W 99.7 99.1‒100.2 Norepinephrine (µg/ml) † 64 D5W 100.1 99.5‒100.6 Norepinephrine (µg/ml) 12 NS 99.5 98.3‒100.7 Norepinephrine (µg/ml) † 64 NS 99.3 98.7‒100.0 Phenobarbitone (mg/ml) 20 NS 99.8 99.2‒100.4 Phenobarbitone (mg/ml) 20 D5W 99.9 99.1‒100.7 Piperacillin/tazobactam (mg/ml) 80 D5W 100.2 99.9‒100.5 Piperacillin/tazobactam (mg/ml) 200 WfI 100.5 99.6‒101.5 Results in bold indicate a statistically significant difference, whereby the 95% CI of the ratio did not span 100% (t-test). Abbreviations: CI, confidence interval; D5W, 5% w/v glucose injection; D10, 10% w/v glucose injection; NS, 0.9% w/v sodium chloride injection; PTX, pentoxifylline; U, undiluted; WfI, water for injection. †Duration of mixture contact time = 2 h (contact time for all other combinations = 1 h). ‡n ≥ 8 (all other combinations n = 4). §Midazolam 5 mg/ml diluted with NS/D5W; all other combinations were dilutions of midazolam 1 mg/ml injection. ¶Pentoxifylline injection was diluted in 0.9% w/v sodium chloride injection to a final concentration of 5 mg/ml to combine with the test drug solution. Dilution in 10% w/v glucose or 0.9% w/v sodium chloride showed modest reductions in concentration ratios (1%‒2% compared to control) and most likely presents no clinically significant risk when morphine is co-administered via Y-site with PTX injection for up to 1 h. 3,4 A confounding result in our current study was the unequivocal compatibility of undiluted calcium gluconate injection (100 mg/ml) with PTX injection (Table 1).