Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil
- PMID: 10719953
- DOI: 10.1097/00000542-200003000-00018
Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil
Abstract
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.
Comment in
-
Location, location, location.Anesthesiology. 2000 Mar;92(3):641-3. doi: 10.1097/00000542-200003000-00005. Anesthesiology. 2000. PMID: 10719940 No abstract available.
Similar articles
-
Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil. An update.Clin Pharmacokinet. 1996 Oct;31(4):275-92. doi: 10.2165/00003088-199631040-00004. Clin Pharmacokinet. 1996. PMID: 8896944 Review.
-
Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 2): effect of epinephrine.Anesthesiology. 2003 Aug;99(2):466-75. doi: 10.1097/00000542-200308000-00030. Anesthesiology. 2003. PMID: 12883421
-
The role of drug-lipid interactions on the disposition of liposome-formulated opioid analgesics in vitro and in vivo.Anesth Analg. 2001 Oct;93(4):928-33. doi: 10.1097/00000539-200110000-00026. Anesth Analg. 2001. PMID: 11574359
-
Effect of (hydroxypropyl)-beta-cyclodextrin on flux of morphine, fentanyl, sufentanil, and alfentanil through the spinal meninges of monkey.J Pharm Sci. 1994 May;83(5):620-2. doi: 10.1002/jps.2600830504. J Pharm Sci. 1994. PMID: 8071807
-
Pharmacokinetics of Fentanyl and Its Derivatives in Children: A Comprehensive Review.Clin Pharmacokinet. 2018 Feb;57(2):125-149. doi: 10.1007/s40262-017-0569-6. Clin Pharmacokinet. 2018. PMID: 28688027 Free PMC article. Review.
Cited by
-
Comparison of clinical effects according to the dosage of sufentanil added to 0.5% hyperbaric bupivacaine for spinal anesthesia in patients undergoing cesarean section.Korean J Anesthesiol. 2012 Oct;63(4):321-6. doi: 10.4097/kjae.2012.63.4.321. Epub 2012 Oct 12. Korean J Anesthesiol. 2012. PMID: 23115684 Free PMC article.
-
A clinical approach to neuraxial morphine for the treatment of postoperative pain.Pain Res Treat. 2012;2012:612145. doi: 10.1155/2012/612145. Epub 2012 Jul 2. Pain Res Treat. 2012. PMID: 23002426 Free PMC article.
-
Characteristics of distribution of morphine and metabolites in cerebrospinal fluid and plasma with chronic intrathecal morphine infusion in humans.Anesth Analg. 2012 Oct;115(4):797-804. doi: 10.1213/ANE.0b013e3182645dfd. Epub 2012 Jul 19. Anesth Analg. 2012. PMID: 22822192 Free PMC article.
-
Intrathecal opioids for combined spinal-epidural analgesia during labour.CNS Drugs. 2003;17(12):889-904. doi: 10.2165/00023210-200317120-00003. CNS Drugs. 2003. PMID: 12962528 Review.
-
The dose response of sufentanil as an adjuvant to ropivacaine in cesarean section for relief from somato-visceral pain under epidural anesthesia in parturients with scarred uterus.Medicine (Baltimore). 2018 Sep;97(38):e12404. doi: 10.1097/MD.0000000000012404. Medicine (Baltimore). 2018. PMID: 30235712 Free PMC article. Clinical Trial.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources