Pharmacokinetics of d-tubocurarine in patients with thermal injury. 1982

J A Martyn, and R S Matteo, and D J Greenblatt, and P W Lebowitz, and J J Savarese

d-Tubocurarine (dTc) requirements are increased following thermal injury. Significant increases in plasma binding only partially account for the altered requirement. To characterize the pharmacokinetic component of the increased requirement, the disposition of dTc was studied in eight patients with burns ranging from 15% to 80% of body surface area and compared with that in six nonburned surgical patients of comparable age and weight. Plasma levels of dTc were measured by radioimmunoassay at multiple times for 24 hours after a single bolus dose. Derived pharmacokinetic parameters were corrected for the predicted (not measured) fraction bound to plasma. The plasma disappearance curve of dTc was explained by linear sum of two or three exponential terms. The unbound central volume of distribution and renal excretion at 24 hours were significantly increased in burned patients (0.11 +/- 0.03 L/kg vs 0.057 +/- 0.015 L/kg, p less than 0.05, 57% +/- 7% vs 40% +/- 11%, p less than 0.05, respectively). On the other hand, comparable elimination half-lives (6.5 +/- 1.8 hr vs 6.2 +/- 1.3 hr, p greater than 0.05), unbound volume of distribution (0.86 +/- 0.2 L/kg vs 0.96 +/- 0.5 L/kg, p greater than 0.05), and intrinsic clearances (1.62 +/- 0.6 ml/kg/min vs 1.56 +/- 0.4 ml/kg/min, p greater than 0.05) were present in burned patients and control patients, respectively. Thus, altered kinetics contributes little to the increased doses required. Similar clearances and elimination half-lives in both groups suggest that loss of dTc through burned tissue is minimal.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D001798 Blood Proteins Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins. Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D002056 Burns Injuries to tissues caused by contact with heat, steam, chemicals (BURNS, CHEMICAL), electricity (BURNS, ELECTRIC), or the like. Burn
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes

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