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)
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee.
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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