Kokki Hannu, Maaroos Martin, Ellam Sten, Halonen Jari, Ojanperä Ilkka, Ranta Merja, Ranta Veli-Pekka, Tolonen Aleksandra, Lindberg Oscar, Viitala Matias, Hartikainen Juha
School of Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Anaesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, KYS, Finland.
Eur J Clin Pharmacol. 2018 Jun;74(6):785-792. doi: 10.1007/s00228-018-2437-1. Epub 2018 Mar 9.
Cardiac surgery and conventional extracorporeal circulation (CECC) impair the bioavailability of drugs administered by mouth. It is not known whether miniaturized ECC (MECC) or off-pump surgery (OPCAB) affect the bioavailability in similar manner. We evaluated the metoprolol bioavailability in patients undergoing CABG surgery with CECC, MECC, or having OPCAB.
Thirty patients, ten in each group, aged 44-79 years, scheduled for CABG surgery were administered 50 mg metoprolol by mouth on the preoperative day at 8-10 a.m. and 8 p.m., 2 h before surgery, and thereafter daily at 8 a.m. and 8 p.m. Blood samples were collected up to 12 h after the morning dose on the preoperative day and on first and third postoperative days. Metoprolol concentration in plasma was analyzed using liquid chromatography-mass spectrometry.
The absorption of metoprolol was markedly reduced on the first postoperative day in all three groups, but recovered to the preoperative level on the third postoperative day. The geometric means (90% confidence interval) of AUC on the first and third postoperative days versus the preoperative day were 44 (26-74)% and 109 (86-139)% in the CECC-group, 28 (16-50)% and 79 (59-105)% in the MECC-group, and 26 (12-56)% and 96 (77-119)% in the OPCAB-group, respectively. Two patients in the CECC-group and two in the MECC-group developed atrial fibrillation (AF). The bioavailability and the drug concentrations of metoprolol in patients developing AF did not differ from those who remained in sinus rhythm.
The bioavailability of metoprolol by mouth was markedly reduced in the early phase after CABG with no difference between the CECC-, MECC-, and OPCAB-groups.
心脏手术及传统体外循环(CECC)会损害口服给药的药物生物利用度。目前尚不清楚小型体外循环(MECC)或非体外循环心脏手术(OPCAB)是否会以类似方式影响生物利用度。我们评估了接受CECC、MECC或OPCAB冠状动脉旁路移植术(CABG)患者的美托洛尔生物利用度。
30例计划行CABG手术的患者,年龄44 - 79岁,每组10例,术前日上午8 - 10点及晚上8点口服50mg美托洛尔,手术前2小时服用,此后每天上午8点和晚上8点服用。在术前日上午服药后12小时内以及术后第1天和第3天采集血样。采用液相色谱 - 质谱法分析血浆中美托洛尔浓度。
所有三组术后第1天美托洛尔的吸收均显著降低,但术后第3天恢复至术前水平。CECC组术后第1天和第3天与术前日相比的AUC几何均值(90%置信区间)分别为44(26 - 74)%和109(86 - 139)%,MECC组为28(16 - 50)%和79(59 - 105)%,OPCAB组为26(12 - 56)%和96(77 - 119)%。CECC组和MECC组各有2例患者发生房颤(AF)。发生AF患者的美托洛尔生物利用度和药物浓度与维持窦性心律患者无差异。
CABG术后早期口服美托洛尔的生物利用度显著降低,CECC组、MECC组和OPCAB组之间无差异。