Sex difference in antipyrine 3-hydroxylation. An in vivo-in vitro correlation of antipyrine metabolism in two rat strains

J. T.M. Buters; J. Reichen

doi:10.1016/0006-2952(90)90314-B

Sex difference in antipyrine 3-hydroxylation. An in vivo-in vitro correlation of antipyrine metabolism in two rat strains

J. T.M. Buters, J. Reichen

University of Bern

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Abstract

Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to which extent antipyrine clearance and metabolite formation in vivo correlate with metabolite formation by microsomal fractions in vitro. The influence of sex was investigated in two rat strains. Antipyrine clearance in saliva was determined in 10-month-old Sprague-Dawley and Dark Agouti rats of either sex. Antipyrine and its metabolites in urine and microsomes were measured by a new HPLC method after solid phase or liquid extraction. Antipyrine clearance was 46% higher in males than in female rats. This was associated with a 40% higher urinary excretion of 3-OH-antipyrine in the male rats, the other metabolites being excreted to a similar extent. This higher production of 3-OH-antipyrine in vivo was paralleled by a higher intrinsic clearance in vitro while no sex difference in intrinsic clearance for the formation of the other metabolites was seen. The correlation between in vivo and in vitro metabolic clearance for 3-OH-antipyrine was good (r = 0.75) but unconvincing for 4-OH- (r = 0.49) and norantipyrine (r = 0.01). This could be due to further metabolism of 4-OH- and norantipyrine.

Original language	English
Pages (from-to)	771-777
Number of pages	7
Journal	Biochemical Pharmacology
Volume	40
Issue number	4
DOIs	https://doi.org/10.1016/0006-2952(90)90314-B
State	Published - 15 Aug 1990
Externally published	Yes

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10.1016/0006-2952(90)90314-B

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@article{8ea926db487946609829813ea51abcb0,

title = "Sex difference in antipyrine 3-hydroxylation. An in vivo-in vitro correlation of antipyrine metabolism in two rat strains",

abstract = "Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to which extent antipyrine clearance and metabolite formation in vivo correlate with metabolite formation by microsomal fractions in vitro. The influence of sex was investigated in two rat strains. Antipyrine clearance in saliva was determined in 10-month-old Sprague-Dawley and Dark Agouti rats of either sex. Antipyrine and its metabolites in urine and microsomes were measured by a new HPLC method after solid phase or liquid extraction. Antipyrine clearance was 46% higher in males than in female rats. This was associated with a 40% higher urinary excretion of 3-OH-antipyrine in the male rats, the other metabolites being excreted to a similar extent. This higher production of 3-OH-antipyrine in vivo was paralleled by a higher intrinsic clearance in vitro while no sex difference in intrinsic clearance for the formation of the other metabolites was seen. The correlation between in vivo and in vitro metabolic clearance for 3-OH-antipyrine was good (r = 0.75) but unconvincing for 4-OH- (r = 0.49) and norantipyrine (r = 0.01). This could be due to further metabolism of 4-OH- and norantipyrine.",

author = "Buters, {J. T.M.} and J. Reichen",

note = "Funding Information: Acknowledgements-This study was supported by SNF grant3 2.9365.87J.. T. M. Buters was partly supportedb y the Berne Liver Foundation. JR was the recipient of a ResearchC areer DevelopmentA ward from SNF 3.731. The HPLC equipmentw as purchasedw ith a grant from the SandozF oundation.T his study would not have been possiblew ithout the expert technicala ssistanceo f MS C. Talos, Mr H. Saegessear nd the carefulw ork with animals of Mr K. Krusch. We thankM S M. Kappelerf or the artwork and MS V. Bidar for secretariaal ssistance.",

year = "1990",

month = aug,

day = "15",

doi = "10.1016/0006-2952(90)90314-B",

language = "English",

volume = "40",

pages = "771--777",

journal = "Biochemical Pharmacology",

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T1 - Sex difference in antipyrine 3-hydroxylation. An in vivo-in vitro correlation of antipyrine metabolism in two rat strains

AU - Buters, J. T.M.

AU - Reichen, J.

N1 - Funding Information: Acknowledgements-This study was supported by SNF grant3 2.9365.87J.. T. M. Buters was partly supportedb y the Berne Liver Foundation. JR was the recipient of a ResearchC areer DevelopmentA ward from SNF 3.731. The HPLC equipmentw as purchasedw ith a grant from the SandozF oundation.T his study would not have been possiblew ithout the expert technicala ssistanceo f MS C. Talos, Mr H. Saegessear nd the carefulw ork with animals of Mr K. Krusch. We thankM S M. Kappelerf or the artwork and MS V. Bidar for secretariaal ssistance.

PY - 1990/8/15

Y1 - 1990/8/15

N2 - Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to which extent antipyrine clearance and metabolite formation in vivo correlate with metabolite formation by microsomal fractions in vitro. The influence of sex was investigated in two rat strains. Antipyrine clearance in saliva was determined in 10-month-old Sprague-Dawley and Dark Agouti rats of either sex. Antipyrine and its metabolites in urine and microsomes were measured by a new HPLC method after solid phase or liquid extraction. Antipyrine clearance was 46% higher in males than in female rats. This was associated with a 40% higher urinary excretion of 3-OH-antipyrine in the male rats, the other metabolites being excreted to a similar extent. This higher production of 3-OH-antipyrine in vivo was paralleled by a higher intrinsic clearance in vitro while no sex difference in intrinsic clearance for the formation of the other metabolites was seen. The correlation between in vivo and in vitro metabolic clearance for 3-OH-antipyrine was good (r = 0.75) but unconvincing for 4-OH- (r = 0.49) and norantipyrine (r = 0.01). This could be due to further metabolism of 4-OH- and norantipyrine.

AB - Antipyrine metabolism depends on at least three isoenzymes of cytochrome P450 forming the main metabolites 3-OH-, 4-OH- and norantipyrine. We investigated to which extent antipyrine clearance and metabolite formation in vivo correlate with metabolite formation by microsomal fractions in vitro. The influence of sex was investigated in two rat strains. Antipyrine clearance in saliva was determined in 10-month-old Sprague-Dawley and Dark Agouti rats of either sex. Antipyrine and its metabolites in urine and microsomes were measured by a new HPLC method after solid phase or liquid extraction. Antipyrine clearance was 46% higher in males than in female rats. This was associated with a 40% higher urinary excretion of 3-OH-antipyrine in the male rats, the other metabolites being excreted to a similar extent. This higher production of 3-OH-antipyrine in vivo was paralleled by a higher intrinsic clearance in vitro while no sex difference in intrinsic clearance for the formation of the other metabolites was seen. The correlation between in vivo and in vitro metabolic clearance for 3-OH-antipyrine was good (r = 0.75) but unconvincing for 4-OH- (r = 0.49) and norantipyrine (r = 0.01). This could be due to further metabolism of 4-OH- and norantipyrine.

UR - http://www.scopus.com/inward/record.url?scp=0025168487&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(90)90314-B

DO - 10.1016/0006-2952(90)90314-B

M3 - Article

C2 - 2386545

AN - SCOPUS:0025168487

SN - 0006-2952

VL - 40

SP - 771

EP - 777

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 4

ER -

Sex difference in antipyrine 3-hydroxylation. An in vivo-in vitro correlation of antipyrine metabolism in two rat strains

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