Effects of Plasma Albumin on the Pharmacokinetics of Esomeprazole in ICU Patients

Abstract

Objectives To evaluate the effects of plasma albumin on pharmacokinetics of esomeprazole in ICU patients. Methods This study was performed in 32 consecutive intensive care unit (ICU) patients. They were divided into two groups according to the plasma albumin levels. Nineteen patients with low plasma albumin levels (<30 g/L; male/female, 12/7) were assigned to low plasma albumin group (LPAG). Thirteen patients with plasma albumin levels >30 g/L (male/female, 9/4) were assigned to high plasma albumin group (HPAG). All patients were received intravenous (IV) of 40 mg esomeprazole in 5 min. Blood samples were collected via basilic vein at different time points and concentrations of esomeprazole were determined by UPLC-MS/MS. Results MRT(0-∞), t1/2, V, CL, and Cmax between two groups were significantly difference (P<0.05). Compared with HPAG, MRT(0-∞), t1/2, and V of esomeprazole in LPAG were increased by 1.42-fold, 1.49-fold, and 1.24-fold, respectively; the maximum drug concentration of esomeprazole in LPAG was decreased to 82.5%. AUC(0-∞) of LPAG was 1.23 times than that of group B. CL in LPAG was 80% of HPAG. There was no statistical difference between the two groups of AUC(0-∞) and CL. Conclusions Some pharmacokinetic parameters of esomeprazole may be changed in ICU patients with low plasma albumin.

Pharmacokinetics of Esomeprazole in Critically Ill Patients

“…The mean t 1/2 of esomeprazole in this study (3.29 h) was much higher than that reported in healthy volunteers (mean, 0.85 h) (10). This observation was consistent with the fact that clearance was reduced while the volume of distribution was increased, which would result in an increased elimination halflife (elimination rate constant k = CL/V) (15). This indicated that the retention time of esomeprazole in critically ill patients is prolonged.…”

“…Blood samples were collected according to the scheduled time and the concentration of esomeprazole in plasma and were determined by UPLC-MS/MS according to a previous method [15]. The chromatographic column was the ACQUITY UPLC BEH C18 column (2.1× 50 mm, 1.7 um).…”

“…Genetic polymorphism of cytochrome CYP2C19 was detected by DNA microarray, which was reported in our previous study (15). In brief, 4 mL of whole blood samples were collected from each patient; the DNA was extracted from the blood using a Blood Genomic DNA Extraction Kit, then the concentration and purity of extracted DNA was determined by spectrophotometry.…”

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“…While the inhibition of CYP3A4 by these compounds (except SA1) can result in a decrease in the metabolism of some toxins, including the parent drug, that leads to its accumulation and an increased risk of toxicity. Moreover, this action can affect the metabolism of other drugs taken simultaneously with these compounds, leading to drug-drug interaction [54]. Additionally, the produced fused coumarin compounds have a very high plasma protein binding capacity which can result in a decrease in the volume of distribution and a reduction in the half-life of these compounds [55].…”

Synthesis and antitumor potential of new 7-halocoumarin-4-acetic acid derivatives

“…Secondly, the ability of the synthesized coumarins to inhibit CYP2C9 may indicate that these coumarins have an antiinflammatory potential since this enzyme metabolizes the arachidonic acid to the inflammatory signaling molecule named eicosatrienoic acid epoxide [20]. Thirdly, the synthesized coumarins have a high capacity for binding with plasma proteins resulting in the dropping of the distribution volume and consequently shorting their half-lives [21]. Finally, the poor inclusion through blood-brain barrier may indicate that these coumarins are free from the neurological side effects and this issue is highly important in the term of toxicity [22].…”