Evaluating a possible pharmacokinetic interaction between remifentanil and esmolol in the rat

被引:30
作者
Haidar, SH
Moreton, JE
Liang, ZM
Hoke, JF
Muir, KT
Eddington, ND
机构
[1] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA
[2] Glaxo Inc, Res Inst, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1021/js970079e
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Remifentanil (Ultiva) is a novel, ultra-short-acting opioid which has recently been approved for use as an analgesic during induction and maintenance of general anesthesia, Esmolol is a short-acting beta-blocker used during surgical procedures to reduce heart rate and blood pressure. Both drugs are metabolized by nonspecific esterases in the blood and other tissues and may be administered concomitantly during surgery. The goal of this study was to determine ii coadministration of esmolol significantly alters the pharmacokinetics of remifentanil in the rat. Two groups of rats were dosed with remifentanil [25 mu g/kg/min (n = 8)] and remifentanil plus esmolol [25 and 200 mg/kg/min (n = 7)] for 20 min. Cardiovascular measurements were collected continuously over the course of the study. Serial blood samples (12) were collected over 25 min into test tubes containing 0.5 mt of acetonitrile, Blood samples were extracted (liquid-liquid) with methylene chloride and then analyzed by a validated GC-MS assay. Compartmental data analysis was performed using PCNONLIN. The mean(+/-SD) for CI and t(1/2) observed in treatment I were 390(+/-98) mL/min/kg and 0.69(+/-0.27) min and in treatment II were 421(+/-164) mL/min/kg and 0.56(+/-0.22) min, respectively. Comparison of clearance, volume of distribution, and terminal half-life between the two groups showed that coadministration of esmolol had no significant do < 0.05) effect on the pharmacokinetics of remifentanil in the rat.
引用
收藏
页码:1278 / 1282
页数:5
相关论文
共 37 条
  • [1] BAILEY PL, 1985, ANESTH ANALG, V64, P48
  • [2] BENNETT GM, 1979, ANESTH ANALG, V58, P179
  • [3] THE PHARMACOKINETICS OF SUFENTANIL IN SURGICAL PATIENTS
    BOVILL, JG
    SEBEL, PS
    BLACKBURN, CL
    OEILIM, V
    HEYKANTS, JJ
    [J]. ANESTHESIOLOGY, 1984, 61 (05) : 502 - 506
  • [4] Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease
    Dershwitz, M
    Hoke, JF
    Rosow, CE
    Michalowski, P
    Connors, PM
    Muir, KT
    Dienstag, JL
    [J]. ANESTHESIOLOGY, 1996, 84 (04) : 812 - 820
  • [5] INITIAL CLINICAL-EXPERIENCE WITH REMIFENTANIL, A NEW OPIOID METABOLIZED BY ESTERASES
    DERSHWITZ, M
    RANDEL, GI
    ROSOW, CE
    FRAGEN, RJ
    CONNORS, PM
    LIBROJO, ES
    SHAW, DL
    PENG, AW
    JAMERSON, BD
    [J]. ANESTHESIA AND ANALGESIA, 1995, 81 (03) : 619 - 623
  • [6] REMIFENTANIL PHARMACOKINETICS AND PHARMACODYNAMICS - A PRELIMINARY APPRAISAL
    EGAN, TD
    [J]. CLINICAL PHARMACOKINETICS, 1995, 29 (02) : 80 - 94
  • [7] THE PHARMACOKINETICS OF THE NEW SHORT-ACTING OPIOID REMIFENTANIL (GI87084B) IN HEALTHY ADULT MALE-VOLUNTEERS
    EGAN, TD
    LEMMENS, HJM
    FISET, P
    HERMANN, DJ
    MUIR, KT
    STANSKI, DR
    SHAFER, SL
    [J]. ANESTHESIOLOGY, 1993, 79 (05) : 881 - 892
  • [8] Remifentanil versus alfentanil - Comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers
    Egan, TD
    Minto, CF
    Hermann, DJ
    Barr, J
    Muir, KT
    Shafer, SL
    [J]. ANESTHESIOLOGY, 1996, 84 (04) : 821 - 833
  • [9] SIMPLE AND RAPID HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR ESMOLOL
    FAN, CD
    ZHAO, H
    CHOW, MSS
    [J]. JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1991, 570 (01): : 217 - 223
  • [10] DESIGN, SYNTHESIS, AND PHARMACOLOGICAL EVALUATION OF ULTRASHORT-ACTING TO LONG-ACTING OPIOID ANALGESICS
    FELDMAN, PL
    JAMES, MK
    BRACKEEN, MF
    BILOTTA, JM
    SCHUSTER, SV
    LAHEY, AP
    LUTZ, MW
    JOHNSON, MR
    LEIGHTON, HJ
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (07) : 2202 - 2208