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Published on: March 23, 2018
The effect of hemodilution by cardiopulmonary bypass on protein binding of olprinone
Tsunehisa Tsubokawa1, Syuichi Ishizuka, Kyoko Fukumoto
1Department of Anesthesiology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. tsune@med.kanazawa-u.ac.jp
Purpose:
Olprinone is a phosphodiesterase type III inhibitor that is often used to increase cardiac output after cardiopulmonary bypass (CPB). Hemodilution by CPB is likely to decrease total olprinone concentration, but it may also increase the free (unbound) concentration of olprinone due to reduced protein binding. The aim of this study was to investigate the effect of hemodilution on the protein binding of olprinone.
Methods:
Eleven patients scheduled for elective cardiac surgery with CPB were enrolled in our study. Olprinone was continuously infused at a rate of 0.2 μg/kg/min from the time of the first surgical incision until the patient arrived at the recovery unit. Protein binding was evaluated twice, just before the start of CPB and at the beginning of withdrawal from CPB. Olprinone concentration and protein binding were determined with high-performance liquid chromatography and ultrafiltration methods, respectively. Olprinone protein binding was also evaluated in vitro.
Results:
Olprinone protein binding to albumin was 63 % in vitro, but it did not bind to alpha-1 acid glycoprotein. Olprinone protein binding in patients before CPB was 81.5 ± 4.3 %, whereas protein binding at withdrawal from CPB was 63.3 ± 14.3 %.
Conclusions:
Unbound olprinone concentration increased by 20 % during CPB, which suggests that the pharmacological effects of olprinone might be enhanced during and after CPB. Close hemodynamic monitoring is necessary to control the effects of olprinone after CPB, because CPB alters olprinone's pharmacokinetics.
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