Effect of (hydroxypropyl)-beta-cyclodextrin on flux of morphine, fentanyl, sufentanil, and alfentanil through the spinal meninges of monkey.
Previous studies have demonstrated that (hydroxypropyl)-beta-cyclodextrin behaves as a slow-release reservoir when used as a vehicle for intrathecal administration of opioids. The goal of the current investigation was to determine if (hydroxypropyl)-beta-cyclodextrin might serve as a slow-release vehicle for epidural opioid administration as well. An in vitro diffusion cell model was used to determine the flux of morphine, fentanyl, alfentanil, and sufentanil through the spinal meninges of Macaque nemestrina monkeys in the absence or presence of varying concentrations of (hydroxypropyl)-beta-cyclodextrin. No concentration of cyclodextrin slowed the flux of any of the opioids through the meninges, indicating that (hydroxypropyl)-beta-cyclodextrin will not behave as a slow-release reservoir for these opioids in the epidural space. This finding suggests that the rate-limiting step in opioid transfer was diffusion through the meninges not dissociation of the opioid cyclodextrin complex. However, (hydroxypropyl)-beta-cyclodextrin significantly increased the flux of sufentanil through the meninges. Since sufentanil's hydrophobicity has previously been shown to impede its meningeal flux, this finding suggests that cyclodextrin effectively decreases sufentanil's hydrophobicity by formation of inclusion complexes in the aqueous environments of the spinal meninges.
Bernards
C M
CM
University of Washington School of Medicine, Department of Anesthesiology, Seattle 98195.
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015760:Alfentanil / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D003505:Cyclodextrins / Q000494:pharmacology*; D004058:Diffusion; D004337:Drug Carriers; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008254:Macaca nemestrina; D008297:Male; D008578:Meninges / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012044:Regression Analysis; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*; D017409:Sufentanil / Q000008:administration & dosage / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D009294:Narcotics; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015760:Alfentanil; D009020:Morphine; D017409:Sufentanil; D005283:Fentanyl