Abstract
Propofol is a short-acting intravenous anesthetic which is rapidly metabolized by glucuronidation and ring hydroxylation catalyzed by cytochrome P450. In clinical trials, it was found that patients receiving both ethanol and propofol injection in the surgery awoke significantly earlier than those who were injected propofol alone. To investigate pharmacokinetic and pharmacodynamic interactions of propofol and ethanol, propofol was injected alone and in combination with ethanol to rabbits. Propofol was injected intravenously at a dose rate of 15 mg kg−1. Ethanol was injected intraperitoneally at a dose rate of 2.5 mg kg−1. An LC assay with native fluorescence detection was developed and validated for determining the concentration of propofol in rabbit plasma and the effect of co-injected ethanol on the plasma pharmacokinetics of propofol in rabbits. Co-injection of ethanol decreased the maximum plasma concentration (C max) and area under the plasma concentration–time curve (AUC0–∞) of propofol by 53.28 and 53.42%, respectively, as compared to the control (P < 0.001). Concomitant ethanol also caused a 66.67% increase in plasma clearance (CL) (P < 0.001). These may partially explain the finding that co-injected ethanol reduced the anesthetic effect of propofol by introducing hepatic microsomal drug-metabolizing enzymes activity in rabbits.
References
Andreoni V, Lynne Hughes JM (2009) Vet Anaesth Analg 36:523–531. doi:10.1111/j.1467-2995.2009.00490.x
Bajpai L, Varshney M, Seubert CN, Dennis DM (2004) J Chromatogr B 810:291–296
Baumgartner CM, Koenighaus H, Ebner JK, Henke J, Schuster T, Erhardt WD (2009) Am J Vet Res 70:1407–1415. doi:10.2460/ajvr.70.11.1407
Myers GJ, Voorhees C, Eke B, Johnstone R (2009) Perfusion 24:349–355. doi:10.1177/0267659109353819
Wilson C, Canning P, Caravati EM (2010) Clin Toxicol 48:165–170. doi:10.3109/15563651003757954
Sneyd JR (1994) Anesth Analg 78:1032–1033
Roschau K, Roschlau WHE (1998) Principles of Medical Pharmacology. Oxford University Press, Oxford 23:290–291
Court MH, Duan SX, Hesse LM, Venkatakrishnan K, Greenblatt DJ (2001) Anesthesiology 94:110–119
Guellec L, Lacarelle B, Villard PH, Point H, Catalin J, Durand A (1995) Anesth Analg 81:855–861
Guitton J, Buronfosse T, Desage M, Flinois JP, Perdrix JP, Brazier JL, Beaune P (1998) Br J Anaesth 80:788–795
Sneyd JR, Simons PJ, Wright B (1994) Xenobiotica 24:1021–1028. doi:10.3109/00498259409043299
Mi W, Sakai T, Kudo T, Kudo M, Matsuki A (2003) J Clin Anesth 15:103–107. doi:10.1016/S0952-8180(02)00510-X
Vuyk J (1997) J Clin Anesth 9:23–26. doi:10.1016/S0952-8180(97)00117-7
Ichinohe T, Aida H, Kaneko Y (2000) Can J Anesth 47:699–704. doi:10.1007/BF03019005
Schraag S, Mohl U, Bothner U, Georgieff M (1999) J Clin Anesth 11:391–396. doi:10.1016/S0952-8180(99)00076-8
Virág J, Kádár E, Szentpétery F, Jakab F (1997) Acta Chir Hung 36:386–388
Livraghi T, Grigioni W, Mazziotti A, Sangalli G, Vettori C (1990) Tumori 76:394–397
Masaki Y, Yamamoto M, Nishimura H, Gomibuchi M, Tanaka S (1997) Kyobu Geka 50:384–388
Goya N, Koga S, Tomizawa Y, Onitsuka S, Yamaguchi Y, Toma H (2007) Int J Urol 14:760–763. doi:10.1111/j.1442-2042.2007.01799.x
Hewitt AJ, Walker KR, Kobus SM, Poklewska-Koziell M, Reynolds JN, Brien JF (2010) Neurotoxicol Teratol 32:164–170. doi:10.1016/j.ntt.2009.12.002
Esfandiari F, Medici V, Wong DH, Jose S, Dolatshahi M, Quinlivan E, Dayal S, Lentz SR, Tsukamoto H, Zhang YH, French SW, Halsted CH (2010) Hepatology 51:932–941. doi:10.1002/hep.23382
Shepard BD, Tuma DJ, Tuma PL (2010) Alcohol Clin Exp Res 34:280–291. doi:10.1111/j.1530-0277.2009.01091.x
Wang Y, Millonig G, Nair J, Patsenker E, Stickel F, Mueller S, Bartsch H, Seitz HK (2009) Hepatology 50:453–461. doi:10.1002/hep.22978
Fassoulaki A, Farinotti R, Servin F, Desmonts JM (1993) Anesth Analg 77:553–556
Acknowledgments
This study was supported by a grant from the National Natural Science Foundation of China (National Natural Science Foundation of China, Beijing, China. Grant No. 30972837).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhai, XJ., Shu, Z., Zhang, SH. et al. Pharmacokinetic and Pharmacodynamic Interactions of Ethanol and Propofol in Rabbits. Chroma 72, 981–985 (2010). https://doi.org/10.1365/s10337-010-1757-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1365/s10337-010-1757-9