Drugs pharmacokinetics in ICU patients: consequences of hypoalbuminemia upon drugs monitoring and dosing scheme

Effects of mild hypoalbuminemia on the pharmacokinetics and pharmacodynamics of dexmedetomidine in patients after major abdominal or thoracic surgery

“…Our study also indicated that the pharmacokinetics of dexmedetomidine was suitable for the 2-compartment model in the patients after major abdominal or thoracic surgery. However, there was a less value of Vss in this study than those reported by other investigators [11,14,15]. A possible explanation is that the subjects are different in these studies.…”

“…Pharmacokinetics of dexmedetomidine has usually been described with a 2-compartment model [11,14,15]. Our study also indicated that the pharmacokinetics of dexmedetomidine was suitable for the 2-compartment model in the patients after major abdominal or thoracic surgery.…”

“…It remains unclear why the pharmacokinetic changes of highly plasma protein-bound drugs, such as dexmedetomidine, are so complex in the patients with hypoalbuminemia. Mimoz et al [14] and Lagneau et al [15] proposed that the shorter t 1/2β and increased Vss could be explained by less protein binding of a highly plasma protein-bound drug in the patients with hypoalbuminemia, making more of it available for elimination and distribution. This claim is most likely not appropriate in regard to elimination of dexmedetomidine.…”

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

“…Valproate is highly protein‐bound to albumin (90% or higher), and the pharmacologically active unbound or free fraction is typically 5–10% of the total valproate concentration but may vary significantly . Valproate protein binding has been understudied; we are aware of only four reported cases of free valproate monitoring in intensive care unit (ICU) patients . Reviews and guidelines recommend monitoring serum valproate concentrations but make sparse or no mention of free serum concentration monitoring or altered protein binding …”

Consideraciones farmacocinéticas en el paciente crítico

“…La primera aporta más volumen donde los fármacos se dispongan. En la segunda, una mayor fracción de fármaco libre podría penetrar a otros tejidos y distribuirse en ellos 2,3,9 .…”