TY - JOUR
T1 - Biotransformation of sevoflurane by rat neonate liver slices
AU - Payne, A. K.
AU - Morgan, S. E.
AU - Gandolfi, A. J.
AU - Brendel, K.
PY - 1995
Y1 - 1995
N2 - Sevoflurane [CF3-CH(OCH2F)-CF3] is biotransformed to inorganic fluoride (F-) and hexafluoroisopropanol, which forms a glucuronide conjugate. Although sevoflurane may be used in newbores without fully developed biotransformation activity, studies were performed using liver slices from rat neonates to determine sevoflurane disposition. Sevoflurane was vaporized in sealed roller culture vials to produce a continuous saturating dose (0.5 mM). After incubation, slices and incubation media were sonicated and centrifuged to remove debits. The supernatant fraction was analyzed for F-, hexafluoroisopropanol, and hexafluoroisopropanol-glucuronide conjugate. The metabolism of sevoflurane by liver slices increased proportionately with time with a stoichiometricproduction (1:1) of hexafluoroisopropanol and F- in all age groups. Only glucuronide conjugates of hexafluoroisopropanol were found. The rate of savoflurane biotransformation measured as fluoride production was similar among slices prepared from all neonate age groups. Although no hexafluoroisopropanol-glucuronide was generated by slices from 4-, 6-, and 8- day-old neonates, by day 21, 17% of the total hexafluoroisopropanol is glucuronidated. This contrasts with the lower levels of free hexafluoroisopropanol typically seen in adults liver slices, wherein 51% of the hexafluoroisopropanol was glucuronidated. These studies indicate that sevoflurane is equally metabolized to hexafluoroisopropanol and F-, but a deficiency in glucuronosyltransferase occurs in neonates.
AB - Sevoflurane [CF3-CH(OCH2F)-CF3] is biotransformed to inorganic fluoride (F-) and hexafluoroisopropanol, which forms a glucuronide conjugate. Although sevoflurane may be used in newbores without fully developed biotransformation activity, studies were performed using liver slices from rat neonates to determine sevoflurane disposition. Sevoflurane was vaporized in sealed roller culture vials to produce a continuous saturating dose (0.5 mM). After incubation, slices and incubation media were sonicated and centrifuged to remove debits. The supernatant fraction was analyzed for F-, hexafluoroisopropanol, and hexafluoroisopropanol-glucuronide conjugate. The metabolism of sevoflurane by liver slices increased proportionately with time with a stoichiometricproduction (1:1) of hexafluoroisopropanol and F- in all age groups. Only glucuronide conjugates of hexafluoroisopropanol were found. The rate of savoflurane biotransformation measured as fluoride production was similar among slices prepared from all neonate age groups. Although no hexafluoroisopropanol-glucuronide was generated by slices from 4-, 6-, and 8- day-old neonates, by day 21, 17% of the total hexafluoroisopropanol is glucuronidated. This contrasts with the lower levels of free hexafluoroisopropanol typically seen in adults liver slices, wherein 51% of the hexafluoroisopropanol was glucuronidated. These studies indicate that sevoflurane is equally metabolized to hexafluoroisopropanol and F-, but a deficiency in glucuronosyltransferase occurs in neonates.
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M3 - Article
C2 - 7600918
AN - SCOPUS:0028949948
VL - 23
SP - 497
EP - 500
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 4
ER -