Lack of effect of spinal anesthesia on drug metabolism.
The effect of spinal anesthesia on drug disposition was determined in six dogs with chronically implanted vascular catheters using propranolol as a model compound. On the first study day, 40 mg of unlabeled propranolol and 200 microCi of [3H]propranolol were injected into the portal and femoral veins respectively. Arterial blood samples were taken for 4 hr for measurement of plasma concentrations of labeled and unlabeled propranolol by high-pressure liquid chromatography (HPLC) and of [3H]propranolol by liquid scintillation counting of the HPLC eluant corresponding to each propranolol peak. Twenty-four hr later, spinal anesthesia was induced with tetracaine (mean dose 20.7 +/- 0.6 mg) with low sacral to midthoracic levels and the propranolol infusions and sampling were then repeated. Spinal anesthesia had no significant effect on either the intrinsic clearance of propranolol (2.01 +/- 0.75 L/min before and 1.9 +/- 0.7 L/min during spinal anesthesia), or on mean hepatic plasma flow (2.01 +/- 0.5 L/min before and 1.93 +/- 0.5 L/min during spinal anesthesia). The systemic clearance and elimination half-life of propranolol were also unchanged by spinal anesthesia (0.9 +/- 0.23 L/min on the first day, 0.7 +/- 0.1 L/min during spinal anesthesia; and 101 +/- 21 min on the first day, 115 +/- 16 min during spinal anesthesia, respectively). The volume of distribution (Vd) of propranolol was similarly unaffected by spinal anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Whelan
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E
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Wood
A J
AJ
Shay
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S
Wood
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M
D000775:Anesthesia, Spinal; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics; D013748:Tetracaine; D014316:Tritium
D004364:Pharmaceutical Preparations; D013748:Tetracaine; D014316:Tritium; D011433:Propranolol