Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction

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  Figure 1:. Renal function effect on ART-123 plasma concentrations during the first 24 hours. The plasma concentrations of ART-123 are presented as mean ± standard deviation. No relevant differences in the ART-123 plasma concentrations were observed among patients with different levels of renal function. Regardless of patient renal function, the plasma concentrations of ART-123 in disseminated intravascular coagulation (DIC) patients administered 380 U/kg of ART-123 were higher than those in the DIC patients administered 130 U/kg of ART-123.

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  Figure 2:. Relationship between 24-h creatinine clearance and urinary excretion rate of ART-123 on Day 1. The urinary excretion rate of ART-123 correlated closely with 24-h creatinine clearance. Urinary excretion rate of ART-123 was calculated by dividing the amount of ART-123 in urine excreted during 24 h after dosing by the amount of initially administered dose.

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  Figure 3:. Relationship between 24-h creatinine clearance and total body clearance of ART-123 on Day 1. Total body clearance decreased in patients with decreased creatinine clearance (r = 0.526). However, the total body clearance in patients with creatinine clearance < 30 ml/min did not decrease. Although some patients received continuous renal replacement therapy (CRRT), it did not affect ART-123 clearance. ○ : CRRT was not performed, • : CRRT was performed. CLtot, total body clearance.

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  Figure 4:. Changes in ART-123 plasma concentration during six days repeated administration. The left side shows the changes in ART-123 plasma concentration in patients administered 380 U/kg ART-123. The right side shows the changes in ART-123 plasma concentration in patients administered 130 U/kg ART-123. ART-123 plasma concentrations were stratified based on the mean 24-h creatinine clearance over six days. During the six-day observation period, 24-h creatinine clearance was measured daily. Among the patients administered 380 U/kg ART-123, one patient was excluded from the analysis of the ART-123 plasma concentrations due to lack of data for 24-h creatinine clearance on Day 6. No relevant differences in the ART-123 plasma concentrations were observed among patients with different levels of renal function. Furthermore, regardless of renal function, ART-123 plasma concentrations in patients administered 380 U/kg of ART-123 were higher than those in patients administered 130 U/kg of ART-123.

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  Figure 5:. Relationship between haemorrhagic adverse events and pharmacokinetic parameters. Maximum plasma concentration (Cmax) or area under the plasma concentration-time curve during the first 144 h (6 days) (AUC0–144) in patients with and without haemorrhagic adverse events was not different. ○ : 380 U/kg, • : 130 U/kg. AEs, adverse events, defined as any undesirable experience regardless of the causal relationship to the study drug.