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Population pharmaco...
Population pharmacokinetic–pharmacodynamic model of subcutaneous bupivacaine in a novel extended-release microparticle formulation
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- Storgaard, Ida Klitzing (författare)
- University of Copenhagen
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- Jensen, Elisabeth Kjær (författare)
- Copenhagen University Hospital
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- Bøgevig, Søren (författare)
- Copenhagen University Hospital
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- Balchen, Torben (författare)
- Copenhagen University Hospital
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- Springborg, Anders Holten (författare)
- Copenhagen University Hospital
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Royal, Mike Allan (författare)
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- Møller, Kirsten (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Werner, Mads Utke (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Copenhagen University Hospital
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- Lund, Trine Meldgaard (författare)
- University of Copenhagen
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(creator_code:org_t)
- Engelska.
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Ingår i: Basic and Clinical Pharmacology and Toxicology. - 1742-7835.
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The objective of this study was to develop a population pharmacokinetic–pharmacodynamic model of subcutaneously administered bupivacaine in a novel extended-release microparticle formulation for postoperative pain management. Bupivacaine was administered subcutaneously in the lower leg to 28 healthy male subjects in doses from 150 to 600 mg in a phase 1 randomized, placebo-controlled, double-blind, dose-ascending study with two different microparticle formulations, LIQ865A and LIQ865B. Warmth detection threshold was used as a surrogate pharmacodynamic endpoint. Population pharmacokinetic–pharmacodynamic models were fitted to plasma concentration-effect-time data using non-linear mixed-effects modelling. The pharmacokinetics were best described by a two-compartment model with biphasic absorption as two parallel absorption processes: a fast, zero-order process and a slower, first-order process with two transit compartments. The slow absorption process was found to be dose-dependent and rate-limiting for elimination at higher doses. Apparent bupivacaine clearance and the transit rate constant describing the slow absorption process both appeared to decrease with increasing doses following a power function with a shared covariate effect. The pharmacokinetic–pharmacodynamic relationship between plasma concentrations and effect was best described by a linear function. This model gives new insight into the pharmacokinetics and pharmacodynamics of microparticle formulations of bupivacaine and the biphasic absorption seen for several local anaesthetics.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- bupivacaine
- local anaesthesia
- pain management
- pharmacokinetics
- PKPD modelling
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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