Mice lacking mdr1-type P-glycoproteins ( mdr1a/1b [ Ϫ / Ϫ ] mice) display large changes in the pharmacokinetics of digoxin and other drugs. Using the kinetics of digoxin in mdr1a/1b ( Ϫ / Ϫ ) mice as a model representing a complete block of P-glycoprotein activity, we investigated the activity and specificity of the reversal agent SDZ PSC833 in inhibiting mdr1-type P-glycoproteins in vivo. Oral PSC833 was coadministered with intravenous
In these children 1-4 years of age, blood concentrations of SDZ ASM 981 during topical treatment with the 1% cream were consistently low even in the children with the most extensive areas treated (up to 69% of their BSA).
Background: Pimecrolimus is a cell-selective inhibitor of inflammatory cytokine release developed specifically for the treatment of inflammatory skin diseases. Aim: The objective of this study was to evaluate blood concentrations and tolerability of pimecrolimus during topical treatment. Methods: Twelve adult patients with extensive atopic dermatitis were enrolled in an open-label, noncontrolled, pharmacokinetic study. The patients were treated twice daily for 3 weeks with pimecrolimus cream 1% on all lesions. Pimecrolimus blood concentrations were measured at regular time points, and the safety and tolerability were monitored throughout the study. Results: In 78% of the 444 blood samples evaluated, pimecrolimus concentrations remained below the limit of quantitation (0.5 ng/ml). The highest concentration measured was 1.4 ng/ml. There was no indication of drug accumulation. Pimecrolimus was well tolerated locally and systemically. Conclusion: The 3-week twice daily treatment with pimecrolimus cream 1% results in consistently low pimecrolimus blood concentrations with no accumulation. Pimecrolimus cream appears suitable for the long-term management of atopic dermatitis.
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