In Vitro Plasma Protein Binding of Neuromuscular Blocking Agents in Different Subpopulations of Patients

In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents.First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young v...

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Published inAnesthesia and analgesia Vol. 81; no. 5; pp. 1019 - 1025
Main Authors Cameron, Maryse, Donati, Francois, Varin, France
Format Journal Article
LanguageEnglish
Published Hagerstown, MD International Anesthesia Research Society 01.11.1995
Lippincott
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ISSN0003-2999
DOI10.1097/00000539-199511000-00022

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Abstract In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents.First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.(Anesth Analg 1995;81:1019-25)
AbstractList In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents. First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents. First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.
In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents. First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.
In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents.First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.(Anesth Analg 1995;81:1019-25)
Author Cameron, Maryse
Varin, France
Donati, Francois
AuthorAffiliation Faculte de Pharmacie, Universite de Montreal (Cameron, Varin), and Department of Anaesthesia, Royal Victoria Hospital and McGill University, Montreal, Quebec, Canada (Donati). This research was supported by the Medical Research Council of Canada. Presented in part at the XII International Congress of Pharmacology, July 24-29, 1994, Montreal, Quebec, Canada. Accepted for publication June 26, 1995. Address correspondence and reprint requests to France Varin, BPharm, PhD, Faculte de Pharmacie, Universite de Montreal, 2900 Edouard Montpetit, Montreal, Quebec, H3C 3J7 Canada
AuthorAffiliation_xml – name: Faculte de Pharmacie, Universite de Montreal (Cameron, Varin), and Department of Anaesthesia, Royal Victoria Hospital and McGill University, Montreal, Quebec, Canada (Donati). This research was supported by the Medical Research Council of Canada. Presented in part at the XII International Congress of Pharmacology, July 24-29, 1994, Montreal, Quebec, Canada. Accepted for publication June 26, 1995. Address correspondence and reprint requests to France Varin, BPharm, PhD, Faculte de Pharmacie, Universite de Montreal, 2900 Edouard Montpetit, Montreal, Quebec, H3C 3J7 Canada
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  organization: Faculte de Pharmacie, Universite de Montreal (Cameron, Varin), and Department of Anaesthesia, Royal Victoria Hospital and McGill University, Montreal, Quebec, Canada (Donati). This research was supported by the Medical Research Council of Canada. Presented in part at the XII International Congress of Pharmacology, July 24-29, 1994, Montreal, Quebec, Canada. Accepted for publication June 26, 1995. Address correspondence and reprint requests to France Varin, BPharm, PhD, Faculte de Pharmacie, Universite de Montreal, 2900 Edouard Montpetit, Montreal, Quebec, H3C 3J7 Canada
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Issue 5
Keywords Human
Obesity
Nutrition disorder
Metabolic diseases
Lipids
In vitro
Blood plasma
Proteins
Biological fixation
Non depolarisant myorelaxant
Interindividual comparison
Hyperlipemia
Pharmacokinetics
Age
Nutritional status
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Snippet In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate...
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SubjectTerms Adult
Age Factors
Aged
Anesthetics. Neuromuscular blocking agents
Atracurium - blood
Biological and medical sciences
Blood Proteins - metabolism
Body Weight
Cholesterol - blood
Female
Humans
Hyperlipidemias - blood
Isoquinolines - blood
Male
Medical sciences
Middle Aged
Mivacurium
Neuromuscular Nondepolarizing Agents - blood
Neuropharmacology
Pharmacology. Drug treatments
Protein Binding
Triglycerides - blood
Vecuronium Bromide - blood
Title In Vitro Plasma Protein Binding of Neuromuscular Blocking Agents in Different Subpopulations of Patients
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