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dc.contributor.authorLusthof KJ
dc.contributor.authorOlling M
dc.contributor.authorKroese ED
dc.contributor.authorBeenen J
dc.contributor.authorPoelen MJ
dc.contributor.authorVaessen HAMG
dc.contributor.authorKamp CG van de
dc.date.accessioned2007-03-09T16:55:21Z
dc.date.available2007-03-09T16:55:21Z
dc.date.issued1993-05-31en_US
dc.identifier658603002en_US
dc.identifier.urihttp://hdl.handle.net/10029/10235
dc.description.abstractEight groups of six male RIV:tox rats received oral and intravenous doses of benzo(a)pyrene (BaP) in a parallel study plan. Intravenously and orally four dose levels were administered. BaF was dissolved in soybean oil for oral administration, and in glycofurol for intravenous administration. The doses were such, that the absolute oral bioavailability could be calculated for two dose levels. The plasma pharmacokinetics of BaP after intravenous administration were described by a two-compartment model. The corresponding kinetic parameters were calculated. The elimination half-life of BaP was approx. 30-60 min. in the period 0-12 h after administration. Therefore, unchanged BaP will not accumulate after repeated administration, when it is administered once daily. The AUC values (area under the plasma concentration-time curve) increased more than proportionally with the oral or intravenous dose. The deviation from linearity was small for the doses used in this study. After oral administration multiple plasma concentration maxima were observed, which may be explained by an interaction of the oil solution with the bile. The absolute oral bioavailability of unchanged BaP was approx. 13% for a dose of 1 mg/kg and approx. 4% for a dose of 5 mg/kg. This does not mean, that the absorption of BaP decreased with increasing doses, because the non-linear increase of the AUC values with the dose may be explained by saturation of metabolism. The kinetic parameters and the oral bioavailability were in the same range as found in the literature for other rat species.
dc.format.extent981000 bytesen_US
dc.format.extent1004209 bytes
dc.format.mimetypeapplication/pdf
dc.language.isonlen_US
dc.publisherRijksinstituut voor Volksgezondheid en Milieu RIVMen_US
dc.relation.ispartofseriesRIVM Rapport 658603002en_US
dc.relation.urlhttp://www.rivm.nl/bibliotheek/rapporten/658603002.htmlen_US
dc.subject.otherbenzo(a)pyreneen
dc.subject.otherpharmacokineticsen
dc.subject.otherbiological availabilityen
dc.subject.otheranimal modelsen
dc.subject.otherbenzo(a)pyreennl
dc.subject.otherfarmacokinetieknl
dc.subject.otherbiobeschikbaarheidnl
dc.subject.otherdiermodelnl
dc.titleFarmacokinetiek en biologische beschikbaarheid van benzo(a)pyreen (BaP) in de RIV:tox raten_US
dc.title.alternative[Pharmacokinetics and biological availability of benzo(a)pyrene (BaP) in the RIV:tox rat.]en_US
dc.typeReport
refterms.dateFOA2018-12-18T08:44:56Z
html.description.abstractEight groups of six male RIV:tox rats received oral and intravenous doses of benzo(a)pyrene (BaP) in a parallel study plan. Intravenously and orally four dose levels were administered. BaF was dissolved in soybean oil for oral administration, and in glycofurol for intravenous administration. The doses were such, that the absolute oral bioavailability could be calculated for two dose levels. The plasma pharmacokinetics of BaP after intravenous administration were described by a two-compartment model. The corresponding kinetic parameters were calculated. The elimination half-life of BaP was approx. 30-60 min. in the period 0-12 h after administration. Therefore, unchanged BaP will not accumulate after repeated administration, when it is administered once daily. The AUC values (area under the plasma concentration-time curve) increased more than proportionally with the oral or intravenous dose. The deviation from linearity was small for the doses used in this study. After oral administration multiple plasma concentration maxima were observed, which may be explained by an interaction of the oil solution with the bile. The absolute oral bioavailability of unchanged BaP was approx. 13% for a dose of 1 mg/kg and approx. 4% for a dose of 5 mg/kg. This does not mean, that the absorption of BaP decreased with increasing doses, because the non-linear increase of the AUC values with the dose may be explained by saturation of metabolism. The kinetic parameters and the oral bioavailability were in the same range as found in the literature for other rat species.


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