Journal article
Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil.
- Ummenhofer WC Department of Anaesthesia, University of Basel, Kantonsspital, Switzerland.
- Arends RH
- Shen DD
- Bernards CM
- 2000-03-17
Published in:
- Anesthesiology. - 2000
Alfentanil
Analgesics, Opioid
Animals
Fentanyl
Injections, Spinal
Microdialysis
Models, Biological
Morphine
Spinal Cord
Sufentanil
Swine
English
BACKGROUND
Despite widespread use, little is known about the comparative pharmacokinetics of intrathecally administered opioids. The present study was designed to characterize the rate and extent of opioid distribution within cerebrospinal fluid, spinal cord, epidural space, and systemic circulation after intrathecal injection.
METHODS
Equal doses of morphine and alfentanil, fentanyl, or sufentanil were administered intrathecally (L3) to anesthetized pigs. Microdialysis probes were used to sample cerebrospinal fluid at L2, T11, T7, T3, and the epidural space at L2 every 5-10 min for 4 h. At the end of the experiment, spinal cord and epidural fat tissue were sampled, and each probe's recovery was determined in vitro. Using SAAM II pharmacokinetic modeling software (SAAM Institute, University of Washington, Seattle, WA), the data were fit to a 16-compartment model that was divided into four spinal levels, each of which consisted of a caternary arrangement of four compartments representing the spinal cord, cerebrospinal fluid, epidural space, and epidural fat.
RESULTS
Model simulations revealed that the integral exposure (area under the curve divided by dose) of the spinal cord (i.e., effect compartment) to the opioids was highest for morphine because of its low spinal cord distribution volume and slow clearance into plasma The integral exposure of the spinal cord to the other opioids was relatively low, but for different reasons: alfentanil has a high clearance from spinal cord into plasma, fentanyl distributes rapidly into the epidural space and fat, and sufentanil has a high spinal cord volume of distribution.
CONCLUSIONS
The four opioids studied demonstrate markedly different pharmacokinetic behavior, which correlates well with their pharmacodynamic behavior.
Despite widespread use, little is known about the comparative pharmacokinetics of intrathecally administered opioids. The present study was designed to characterize the rate and extent of opioid distribution within cerebrospinal fluid, spinal cord, epidural space, and systemic circulation after intrathecal injection.
METHODS
Equal doses of morphine and alfentanil, fentanyl, or sufentanil were administered intrathecally (L3) to anesthetized pigs. Microdialysis probes were used to sample cerebrospinal fluid at L2, T11, T7, T3, and the epidural space at L2 every 5-10 min for 4 h. At the end of the experiment, spinal cord and epidural fat tissue were sampled, and each probe's recovery was determined in vitro. Using SAAM II pharmacokinetic modeling software (SAAM Institute, University of Washington, Seattle, WA), the data were fit to a 16-compartment model that was divided into four spinal levels, each of which consisted of a caternary arrangement of four compartments representing the spinal cord, cerebrospinal fluid, epidural space, and epidural fat.
RESULTS
Model simulations revealed that the integral exposure (area under the curve divided by dose) of the spinal cord (i.e., effect compartment) to the opioids was highest for morphine because of its low spinal cord distribution volume and slow clearance into plasma The integral exposure of the spinal cord to the other opioids was relatively low, but for different reasons: alfentanil has a high clearance from spinal cord into plasma, fentanyl distributes rapidly into the epidural space and fat, and sufentanil has a high spinal cord volume of distribution.
CONCLUSIONS
The four opioids studied demonstrate markedly different pharmacokinetic behavior, which correlates well with their pharmacodynamic behavior.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1097/00000542-200003000-00018
- PMID 10719953
- Persistent URL
- https://sonar.ch/global/documents/183300
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