Interactions between epidurally and intrathecally administered sufentanil and bupivacaine in hydroxypropyl-beta-cyclodextrin in the rat.
The interaction between inactive doses of the opioid sufentanil and the local anesthetic bupivacaine after complexation in various concentrations of hydroxypropyl-beta-cyclodextrin (HP-B-CD) were studied after epidural and intrathecal administration in the rat. Whereas 0.125 microgram sufentanil and 80 micrograms bupivacaine produced only limited effects, a combination of the two compounds resulted in a profound surgical analgesia in all rats tested after epidural administration. Also intrathecally, a clear potentiation was present. The complexation of the same doses of sufentanil plus bupivacaine in HP-B-CD increased the duration of analgesia. Epidurally, a maximal potentiation of analgesia was present at 0.125 microgram sufentanil plus 80 micrograms bupivacaine in 20% HP-B-CD. Intrathecally, maximal potentiation of the analgesic activity was present starting from a complexation of both drugs in 10% hydroxypropyl-beta-cyclodextrin. Higher concentrations of hydroxypropyl-beta-cyclodextrin did not significantly further increase the duration of analgesia. These results indicate that for both routes of spinal administration, the complexation of sufentanil plus bupivacaine in HP-B-CD can produce a longer analgesia than either plain sufentanil, sufentanil combined with bupivacaine or sufentanil alone in HP-B-CD. The complexation of sufentanil plus bupivacaine in HP-B-CD did not diminish the increased safety observed to occur after complexation of sufentanil in HP-B-CD and after combination of sufentanil plus bupivacaine.
Meert
T F
TF
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
Melis
W
W
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000700:Analgesics / Q000378:metabolism*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000378:metabolism*; D003505:Cyclodextrins / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D005283:Fentanyl / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D007268:Injections, Epidural; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017409:Sufentanil; D013997:Time Factors; D047392:beta-Cyclodextrins
D000700:Analgesics; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017409:Sufentanil; D005283:Fentanyl; D002045:Bupivacaine