Abstract:
BACKGROUND:The pharmacokinetics of epidurally administered drugs has been the subject of many studies, yet drug concentration in the epidural space has never been measured. This study was undertaken to characterize the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids on the basis of measurement of drug concentration in each of these compartments after epidural administration. METHODS:Morphine plus alfentanil, fentanyl, or sufentanil were administered epidurally in anesthetized pigs. Microdialysis was used to sample the epidural space and the cerebrospinal fluid for measurement of opioid concentration over time. Plasma samples were obtained from the central venous plasma and the epidural venous plasma. These data were used to calculate relevant pharmacokinetic parameters, including mean residence time, elimination half-lives, areas under the concentration versus time curves, clearance, and volume of distribution for each opioid in each compartment. RESULTS:Some of the more important findings were that the cerebrospinal fluid and plasma pharmacokinetics of the opioids did not parallel their epidural pharmacokinetics and that their hydrophobic character governed multiple aspects of their lumbar epidural pharmacokinetics. CONCLUSIONS:The findings indicate that the spinal pharmacokinetics of these drugs are complex and, in some ways, counterintuitive. Also, the bioavailability of opioids in the cerebrospinal fluid and epidural space is determined primarily by their hydrophobicity, with less hydrophobic drugs having greater bioavailability.
journal_name
Anesthesiologyjournal_title
Anesthesiologyauthors
Bernards CM,Shen DD,Sterling ES,Adkins JE,Risler L,Phillips B,Ummenhofer Wdoi
10.1097/00000542-200308000-00029subject
Has Abstractpub_date
2003-08-01 00:00:00pages
455-65issue
2eissn
0003-3022issn
1528-1175pii
00000542-200308000-00029journal_volume
99pub_type
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