Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients.

Background: Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (C u ), total plasma (C p ), and whole-blood (C wb ) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices.

A glucocorticoid spike derails muscle repair to heterotopic ossification after spinal cord injury.

Why severe injury to the central nervous system (CNS) triggers the development of large neurogenic heterotopic ossifications (NHOs) within periarticular muscles remains unknown. We report that spinal cord injury (SCI) triggers a rapid corticosterone spike in mice, which is causal for NHO development because treatments with corticosterone or the synthetic glucocorticoid (GC) receptor (GR) agonist dexamethasone are sufficient to trigger heterotopic ossification and upregulate the expression of osteoinductive and osteogenic differentiation genes in injured muscles even without SCI. The central role for GR signaling in causing NHO is further demonstrated in mice deleted for the GR gene (Nr3c1), which no longer develop NHO after SCI.

Serum ganciclovir drug exposure in children receiving standard ganciclovir dosing.

Intravenous ganciclovir (GCV) is used for the treatment of cytomegalovirus (CMV) infection in immunocompromised children. Although the therapeutic target for treatment is unclear, studies have shown a serum area under the concentration-time curve (AUC) ≥40 mg/L·h correlates with effective CMV prevention. This study aimed to externally validate existing GCV population pharmacokinetic (PopPK) models and develop a model if needed and evaluate the serum AUC achieved with standard GCV dosing and propose an optimized dosing strategy for immunocompromised children.