Department of Anesthesiology

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Pharmacokinetics of d-tubocurarine in patients with thermal injury.

TitlePharmacokinetics of d-tubocurarine in patients with thermal injury.
Publication TypeJournal Article
Year of Publication1982
AuthorsMartyn JA, Matteo RS, Greenblatt DJ, Lebowitz PW, Savarese JJ
JournalAnesth Analg
Volume61
Issue3
Pagination241-6
Date Published1982 Mar
ISSN0003-2999
KeywordsAdult, Aged, Blood Proteins, Burns, Child, Female, Half-Life, Humans, Kinetics, Male, Middle Aged, Models, Biological, Protein Binding, Tubocurarine
Abstract

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.

Alternate JournalAnesth. Analg.
PubMed ID7199837
Grant List09069 / / PHS HHS / United States
GM 21700 / GM / NIGMS NIH HHS / United States
MH 34223 / MH / NIMH NIH HHS / United States