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Titolo:
BUCCAL ABSORPTION OF ETOMIDATE FROM A SOLID FORMULATION IN DOGS
Autore:
ZHANG J; MALAND L; HAGUE B; NIU S; ROBERTSON S; COLEMAN D; STANLEY TH; STREISAND JB;
Indirizzi:
UNIV UTAH,HLTH SCI CTR,DEPT ANESTHESIOL,50 N MED DR SALT LAKE CITY UT84132 ANESTA CORP SALT LAKE CITY UT 00000
Titolo Testata:
Anesthesia and analgesia
fascicolo: 5, volume: 86, anno: 1998,
pagine: 1116 - 1122
SICI:
0003-2999(1998)86:5<1116:BAOEFA>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
DECONVOLUTION METHOD; PLASMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
J. Zhang et al., "BUCCAL ABSORPTION OF ETOMIDATE FROM A SOLID FORMULATION IN DOGS", Anesthesia and analgesia, 86(5), 1998, pp. 1116-1122

Abstract

Etomidate is typically administered IV for the induction of general anesthesia. We believe that oral transmucosal absorption may extend etomidate's use to premedication and conscious sedation. Our objective was to study the oral mucosal absorption kinetics and bioavailability ofetomidate ina solid dose form in dogs. A solid dose form containing 50 mg of etomidate in sorbitol for buccal administration was prepared. Each dog was administered both IV etomidate and buccal etomidate on separate days. Serum etomidate concentrations after IV administration were fit to a two-compartment pharmacokinetic model. The rates at which etomidate enters the systemic circulation via buccal mucosal absorption were calculated from serum concentrations from mucosal and IV administrations using model-dependent constrained numerical deconvolution. The apparent permeability coefficient and bioavailability were also determined. The mean (+/- SD) maximal serum etomidate concentration afterbuccal mucosal absorption from the 50-mg dose unit was 239 +/- 79 ng/mL. The time to reach maximal serum concentration was 12.5 +/- 1.8 min. Peak absorption rate of etomidate into the systemic circulation was 832 +/- 417 mu g/min For all dogs, 90% or more of the absorption via buccal mucosa took place during the period in which the drug was in contact with the mucosa (15 min). The apparent transbuccal mucosal permeability coefficient was 9.1 +/- 4.2 x 10(-4) cm/s, higher than values of any other compounds examined. Bioavailability calculated using the area under the serum etomidate concentration versus time curve method and the deconvolution method was 13.6% +/- 10.7% and 16.6% +/- 7.6%, respectively. In conclusion etomidate is highly permeable through the canine buccal mucosa. Implications: Etomidate is highly permeable through the canine buccal mucose. Both the onset and the termination of buccal mucosal absorption of etomidate are rapid, which suggests that titratable delivery of etomidate may be possible by buccal administration.

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Documento generato il 19/09/20 alle ore 15:28:09