title: Effect of the paclitaxel vehicle, Cremophor EL, on the pharmacokinetics of doxorubicin and doxorubicinol in mice.
abstract: The effect of the paclitaxel vehicle Cremophor on the pharmacokinetics of doxorubicin and doxorubicinol was studied in two groups of mice given intravenously either 2.5 ml kg-1 Cremophor or saline followed 5 min later by 10 mg kg-1 doxorubicin. In each group three mice were sacrificed at ten time points and doxorubicin and doxorubicinol were measured in plasma by high-performance liquid chromatography (HPLC). With Cremophor present, doxorubicin AUC increased from 1420+/-440 to 2770+/-660 ng h ml(-1) (P<0.05) and doxorubicinol AUC increased from 130+/-76 to 320+/-88 ng h ml(-1) (p<0.05). Neither the terminal elimination half-lives nor the doxorubicinol-doxorubicin AUC ratio changed in the presence of Cremophor, suggesting a lack of a direct effect on drug metabolism. The possibility exists the Cremophor may change the pharmacokinetics of both paclitaxel and other drugs given concurrently.
authors.affiliation: Division of Research, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.
authors.forename: L K
authors.initials: LK
authors.lastname: Webster
authors.forename: E J
authors.initials: EJ
authors.lastname: Cosson
authors.forename: K H
authors.initials: KH
authors.lastname: Stokes
authors.forename: M J
authors.initials: MJ
authors.lastname: Millward
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel; D012997:Solvents; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D012997:Solvents; C000515:cremophor EL; D004317:Doxorubicin; C010013:adriamycinol; D017239:Paclitaxel; D005990:Glycerol