Nonlinear accumulation in the brain of the new taxoid TXD258 following saturation of P-glycoprotein at the blood-brain barrier in mice and rats.

1. TXD258, a new taxoid antitumor agent, is a poor substrate for the P-glycoprotein (P-gp) in Caco-2 cells. In this study, we investigated the amount of drug accumulating in the brains of rats and mice under a variety of conditions (dose and infusion time, species and plasma concentration) using conventional in vivo pharmacokinetic techniques and in situ brain perfusion.

In vitro binding and partitioning of irinotecan (CPT-11) and its metabolite, SN-38, in human blood.

The binding of CPT-11 and SN-38 to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. In plasma, CPT-11 was 66-60% bound in the range 100-4000 ng/ml and SN-38 was 94-96% bound in the range 50-200 ng/ml.

Quantitative distribution studies in animals: cross-validation of radioluminography versus liquid-scintillation measurement.

The results of a cross-validation of the radioluminography (RLG) and liquid scintillation counting (LSC) methods are presented. The methods for the determination of radioactivity concentrations were compared in 16 organs, after administration of (14)C-labeled substances to rats. LSC measurements of two kinds were used as reference methods for RLG: (1) quantitative determination of radioactivity after conventional dissection (interindividual comparison) and (2) quantitative determination of radioactivity in tissue punches taken from the whole-body sections after they had undergone RLG measurement (intraindividual comparison).

Sensitivity of radioluminography using (14)C-labeled tracers in whole-body sections of rats.

Radioluminography using photostimulated luminescence recently became popular for the quantitation of radioactivity in whole-body sections. In order to estimate the limits of the method, the sensitivity was investigated using routinously prepared blood standards with known amounts of radioactivity. The blood standards underwent the typical steps similar to conventional whole-body autoradiography including freezing, sectioning, and lyophilizing.

Age-dependent variation of selenium-75 biokinetics in rat.

Substantial levels of selenium-79 (79Se) in radioactive waste from the nuclear fuel cycle, may result in a significant collective dose commitment following release into the environment. Few data are available from which the effective dose equivalent among subgroups of the general population can be made. Accordingly, whole body retention and organ content were studied in neonate, adult and pregnant rat following oral contamination with 75Se.