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Pharmacokinetics of Morphine and Morphine-6-Glucuronide During Postoperative Pain Therapy in Cardiac Surgery Patients.
Ihmsen, Harald; Schüttler, Jürgen; Jeleazcov, Christian.
Afiliación
  • Ihmsen H; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstrasse 12, 91054, Erlangen, Germany. harald.ihmsen@uk-erlangen.de.
  • Schüttler J; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstrasse 12, 91054, Erlangen, Germany.
  • Jeleazcov C; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstrasse 12, 91054, Erlangen, Germany.
Eur J Drug Metab Pharmacokinet ; 46(2): 249-263, 2021 Mar.
Article en En | MEDLINE | ID: mdl-33547559
BACKGROUND AND OBJECTIVE: Morphine is a standard analgesic drug for postoperative pain therapy. This study aimed to evaluate the pharmacokinetics of morphine and its active metabolite morphine-6-glucuronide (M6G) in cardiac surgery  patients during postoperative analgesia. METHODS: Twenty-five adult patients undergoing cardiac surgery received postoperative pain therapy by patient-controlled analgesia with intravenous bolus doses of morphine. Plasma concentrations of morphine and M6G were determined from arterial samples. Population pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. RESULTS: Data from twenty-one patients (aged 44-79 years) were analyzed. Pharmacokinetics were best described by a three-compartment model for morphine and a two-compartment model for M6G, linked by a transit compartment. Mean (±SD) population estimates for morphine were: clearance (CL) = 1.35±0.40 L/min, central volume of distribution (V1) = 8.1±2.2 L, steady-state volume of distribution (Vss) = 207±83 L, terminal elimination half-life (T1/2γ) = 177±50 min. Clearance of morphine was proportional to cardiac output. Mean (±SD) population estimates for M6G were: CL = 0.098±0.037 L/min, V1 = 5.5±0.8 L, Vss = 15.8±0.8 L, T1/2ß = 227±74 min. The time to peak concentration of M6G after a bolus dose of morphine was 53±20 min. Clearance of M6G was proportional to estimated glomerular filtration rate. CONCLUSIONS: The pharmacokinetics of morphine and M6G in pain therapy of cardiac surgery  patients could be well described by standard compartmental models. Cardiac output was identified as a significant covariate for morphine clearance, whereas renal function was identified as the most significant covariate for clearance of M6G. These effects should be particularly considered if morphine is administered as a continuous infusion. The developed pharmacokinetic model also enables patient-controlled target-controlled infusion for pain therapy with morphine. TRIAL REGISTRATION: Clinical Trials NCT02483221 (June 26, 2015).
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Dolor Postoperatorio / Analgésicos Opioides / Modelos Biológicos / Morfina / Derivados de la Morfina Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Drug Metab Pharmacokinet Año: 2021 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Dolor Postoperatorio / Analgésicos Opioides / Modelos Biológicos / Morfina / Derivados de la Morfina Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Drug Metab Pharmacokinet Año: 2021 Tipo del documento: Article País de afiliación: Alemania