Removal of anti-Galalpha1,3Gal xenoantibodies with an injectable polymer.

Preformed and elicited Ab's against the Galalpha1,3Gal terminating carbohydrate chains (alphaGal Ab's) are the primary cause of hyperacute and acute vascular xenograft rejection in pig-to-primate transplantation. alphaGal Ab's are produced by long-lived Ab-producing cells that are not susceptible to pharmacological immunosuppression. We reasoned that antigen-specific elimination of alphaGal Ab's might be achieved in vivo by systemic administration of nonimmunogenic polyvalent alphaGal structures with high avidity for alphaGal Ab's.

Low systemic exposure after repeated topical application of Pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis.

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.

Pharmacokinetics of cyclosporine in monkeys after oral and intramuscular administration: relation to efficacy in kidney allografting.

In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate (Neoral) was lower than that upon intramuscular administration. For oral administration, mean values ( +/- SD) of Cmax, 24-h area-under-the curve (AUC) and 24-h trough level, all normalized for a 1 mg/kg dose, were 20 +/- 9 ng x kg/mg x ml, 210 +/- 70 ng x h x kg/mg x ml and 2.6 +/- 0.

First experience of topical SDZ ASM 981 in children with atopic dermatitis.

Background: SDZ ASM 981 is a selective inhibitor of inflammatory cytokine release under development for the topical treatment of atopic dermatitis.

Objectives: This first paediatric study was designed to measure the systemic exposure to SDZ ASM 981 in young children with atopic dermatitis treated on extensive skin areas.

Methods: Children 1-4 years of age referred to a tertiary care centre for their atopic dermatitis were treated twice daily for 3 weeks with 1% SDZ ASM 981 cream.

Side effects of brequinar and brequinar analogues, in combination with cyclosporine, in the rat.

Brequinar is an immunosuppressant with the potential to be combined with cyclosporine in synergistic combination therapy. The drug tends to accumulate when given daily per os, and pharmacokinetic interaction with cyclosporine appears to enhance toxicity. Analogues with similar immunosuppressive activity have been identified at Du Pont Merck Pharmaceutical Co.

Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833.

Mice lacking mdr1-type P-glycoproteins (mdr1a/1b [-/-] mice) display large changes in the pharmacokinetics of digoxin and other drugs. Using the kinetics of digoxin in mdr1a/1b (-/-) 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 [3H]digoxin to wild-type and mdr1a/1b (-/-) mice.