| Summary: | Hypoxemia is known to induce various physiological changes which can result in
pharmacokinetic changes. To examine the effect of acute, moderate hypoxemia in
metoclopramide (MCP) pharmacokinetics, a continuous infusion [14 hours] of MCP was
administered during pre-hypoxemia (2hr), hypoxemia (6hr) and post-hypoxemia (6hr) in
non-pregnant sheep. Hypoxemia was achieved by lowering the ewe's inspired O2
concentration. During the experiment, arterial blood and urine samples were collected.
MCP and its mono- and di-deethylated metabolites were measured in these fluid samples
using a gas chromatography-mass selective detector (GC-MSD) method. Steady-state
concentrations of MCP were achieved in each of the three periods. During hypoxemia,
MCP plasma steady-state concentration increased significantly from 50.72 ± 1.06 to
63.62 ± 1.79 ng/mL, and later decreased to 55.83 ± 1.15 ng/mL during the posthypoxemic
recovery period. Plasma mdMCP concentration (32.78 ± 1.73 ng/mL) also
increased, compared to the control group (21.20 ± 1.39 ng/mL), during hypoxemia and
the subsequent normoxemic period. Renal excretion of MCP and its metabolites
significantly decreased during hypoxemia. Increased urine flow with decreased urine
osmolality was also observed. Thus the results indicate that acute, moderate hypoxemia
affects MCP pharmacokinetics. === Pharmaceutical Sciences, Faculty of === Graduate
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