Validation of an HPLC method for analysis of DB-67 and its water soluble prodrug in mouse plasma.

A method for the quantitation of DB-67 ((20S)-10-hydroxy-7-tert-butyldimethylsilylcamptothecin) lactone and carboxylate in mouse plasma has been developed, validated, and applied in pharmacokinetic studies. The analytes were separated by reversed-phase chromatography with fluorescence detection. Validation demonstrated the selectivity and specificity for the carboxylate and lactone, with linearity between 1-300ng/mL and 2.

Dependence of nelfinavir brain uptake on dose and tissue concentrations of the selective P-glycoprotein inhibitor zosuquidar in rats.

Most reverse transcriptase and protease inhibitors used in highly active antiretroviral therapy for treating human immunodeficiency virus (HIV) infections exhibit poor penetration into the brain, raising the concern that the brain may be a sanctuary site for the development of resistant HIV variants. This study explores the relationship between the dose and plasma and brain concentrations of zosuquidar and the effect of this selective P-glycoprotein inhibitor on central nervous system penetration of the HIV protease inhibitor nelfinavir maintained at steady state by intravenous infusions in rats. Nelfinavir was infused (10 mg/kg/h) for up to 10 h with or without concurrent administration of an intravenous bolus dose of 2, 6, or 20 mg/kg zosuquidar given at 4 h.