“Purpose: The potent immunosuppressive
effect of systemic tacrolimus is limited by the high incidence of severe adverse effects, including nephrotoxicity and hypertension. Intravesical application of tacrolimus is hindered by its poor aqueous solubility, justifying the search for novel delivery platforms such as liposomes. We evaluated the pharmacokinetics of tacrolimus encapsulated in liposomes (lipo-tacrolimus), which is being developed as a potential orphan drug indication for hemorrhagic cystitis.
Materials and Methods: A single dose of lipo-tacrolimus was instilled in the bladder with the rat under anesthesia. Also, tacrolimus was instilled intravesically or injected AZD1080 solubility dmso intraperitoneally in other rat groups. The Adriamycin molecular weight tacrolimus dose was constant in all formulations at 200 mu g/ml. At different times blood, urine and bladder samples were collected and stored at -80C until analysis. Tacrolimus levels in samples were analyzed using microparticle enzyme immunoassay II.
Results: The AUC of lipo-tacrolimus in serum at 0 to 24 hours was significantly lower than that of tacrolimus instillation or injection. Noncompartmental pharmacokinetic data analysis revealed maximum concentration of lipo-tacrolimus
and tacrolimus in serum and urine at 1 and at 2 hours, respectively. Urine AUC((0-24)) after intravesical administration was significantly higher than in the intraperitoneal group (p < 0.05). Bladder tacrolimus AUC((0-24)) did not differ significantly between the groups.
Conclusions: Single dose pharmacokinetics revealed that bladder instillation of liposome encapsulated tacrolimus significantly decreased systemic exposure to instilled tacrolimus as well as vehicle related toxicity. Intravesical liposomal tacrolimus Electron transport chain may be a promising approach as an orphan drug indication for hemorrhagic cystitis.”
“Staphylococcus aureus is both a prominent cause of nosocomial infections with significant morbidity and mortality and a commensal with nasal carriage in around 30% of the population. The rapid spread of multi-resistant strains necessitates novel therapeutic strategies, a challenging
task because the species S. aureus and the host response against it are highly variable. In a prospective study among 2023 surgical and non-surgical patients, 12 patients developed S. aureus bacteremia. They were analysed in detail using a personalized approach. For each patient, the extracellular proteins of the infecting S. aureus strain were identified and the developing antibody response was assessed on 2-D immunoblots. S. aureus carriers showed clear evidence of strain-specific pre-immunization. In all immune-competent bacteremia patients, antibody binding increased strongly, in most cases already at diagnosis. In endogenous infections, the pattern of antibody binding was similar to the pre-infection pattern. In exogenous infections, in contrast, the pre-infection pattern was radically altered with the acquisition of new specificities.