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Arzneimittelforschung 2011; 61(10): 545-552
DOI: 10.1055/s-0031-1300552
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Influence of demographic factors, basic blood test parameters and opioid type on propofol pharmacokinetics and pharmacodynamics in ASA I–III patients

Agnieszka Bienert
1   Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
,
Paweł Wiczling
2   Department of Biopharmaceutics and Pharmacodynamics, Medical Univeristy of Gdansk, Gdańsk, Poland
,
Czesław Żaba
3   Department of Forensic Medicine, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
,
Zbigniew Żaba
4   Department of Anesthesiology, Intensive Care and Pain, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
,
Anna Wolc
5   Department of Genetics and Animal Breeding Poznan University of Life Sciences, Poznań, Poland
,
Ryszard Marciniak
6   Department of General, Gastroenterological and Endocrinological Surgery, Karol Marcinkowski, University of Medical Sciences, Poznań, Poland
,
Edmund Grześkowiak
1   Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Poznań, Poland
,
Krzysztof Kusza
7   Department of Anaesthesiology and Intensive Therapy Collegium Medicum, Nicolaus Copernicus University, Torun, Poland
› Author Affiliations
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Publication History

Publication Date:
01 February 2012 (online)

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Abstract

The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol (CAS 2078-54-8) during total intravenous anesthesia monitored by spectral frequency index (SFx). Twenty-eight patients of ASA physical status I–III (ASA: American Society of Anesthesiologists) scheduled for laparoscopic cholecystectomy were included. In group I an anesthesia was induced with a bolus of propofol (2 mg/kg) and remifentanil (CAS 132875-61-7) (1.0 µg/kg), followed by a continuous infusion of remifentanil. In group II, an alfentanil (CAS 71195-58-9) (10 µg/kg) bolus dose was followed by a continuous infusion of alfentanil. The general anesthetic technique included propofol, opioid and muscle relaxant. During anesthesia, the propofol infusion rate (3–8 mg/kg/h) was adjusted to the SFx value. Venous blood samples were collected from the patients during 240 min after termination of the infusion.

A two compartment model was used to describe propofol PK. A standard effect compartment model was used to describe the delay between the effect and the concentration of propofol. The SFx index was linked to the effect site concentrations through a sigmoidal Emax model. The influence of continuous (body weight, age, blood pressure, heart rate and blood oxygenation, serum protein, the erythrocyte count, hemoglobin and hematocrit, serum creatinine and creatinine clearance) and categorical (gender and the type of opioid) covariates on the pharmacokinetic and pharmacodynamic parameters was investigated. PK/PD analysis was performed using NONMEM. All the screened covariates did not influence propofol PK and PD, except of the opioid type. The central compartment volume of propofol was larger in the presence of remifentanil than in the presence of alfentanil.

Key words

Blood morphology - Opioid - Pharmacodynamics - Pharmacokinetics - Propofol
 

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