Simple Formula for Predicting Drug Removal Rates During Hemodialysis

Urata, Motoki; Narita, Yuki; Fukunaga, Masaki; Kadowaki, Daisuke; Hirata, Sumio

doi:10.1111/1744-9987.12675

Cited by 7 publications

(14 citation statements)

References 21 publications

(21 reference statements)

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“…This effect is presumably attributed to the lack of available data on the potential dialysis of tranexamic acid. On the other hand, the molecular weight of 157.2 Da, the volume of distribution of 1.0 L/kg, and the plasma protein binding of approximately 3% at therapeutic levels may suggest effective removal through dialysis [16,17,19].…”

Section: Discussionmentioning

confidence: 99%

Oral tranexamic acid combined with low molecular weight heparin only during dialysis sessions successfully controlled chronic disseminated intravascular coagulation associated with aortic aneurysm and aortic dissection in a dialysis patient: a case report with literature review

Eguchi¹

2019

Ren Replace Ther

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Section: Discussionmentioning

confidence: 99%

Oral tranexamic acid combined with low molecular weight heparin only during dialysis sessions successfully controlled chronic disseminated intravascular coagulation associated with aortic aneurysm and aortic dissection in a dialysis patient: a case report with literature review

Eguchi¹

2019

Ren Replace Ther

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“…2 Infectious Diseases Department, Hospital Universitari Germans Trias i Pujol, Ctra de Canyet, s/n, 08916 Badalona, Barcelona, Spain. 3 Universitat Autònoma de Barcelona, Barcelona, Spain. 4 Nephrology Department, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.…”

Section: Acknowledgementsmentioning

confidence: 99%

“…Drug removal by hemodialysis is an essential factor in determining different dosing regimens. However, the pharmacokinetics of many drugs in patients on hemodialysis has been poorly studied, and information about their hemodialyzability remains scant [3][4][5]. In addition, HIV patients with PAH or ESRD are frequently affected by other co-morbidities that require specific therapies.…”

Section: Introductionmentioning

confidence: 99%

Ambrisentan use in a HIV-1 infected patient with end-stage renal disease and pulmonary hypertension: minimal removal by hemodialysis - a case report

et al. 2020

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Background: Ambrisentan is a selective endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension (PAH). Little is known about ambrisentan removal by hemodialysis in patients with end-stage renal disease (ESRD). Case presentation: A 53-year-old woman with HIV/hepatitis C virus (HCV) co-infection, PAH and ESRD on regular hemodialyis was admitted in our hospital due to refractory heart failure while on treatment with bosentan (125 mg twice daily) and tadalafil (20 mg once daily) for PAH and antiretroviral treatment (cART) including darunavir/ cobicistat (800/150 mg once daily). Excessive exposure to bosentan due to drug interactions between bosentan and darunavir/cobicistat was suspected. Bosentan was replaced by ambrisentan, with progressive improvement in her clinical condition. Pre-and postdialyzer cocentrations of ambrisentan in plasma were determined and hemodialysis extraction ratio for ambrisentan was 2%. Conclusions: Our results suggest that hemodialysis results in minimal ambrisentan removal, and therefore no specific ambrisentan dosage adjustment seems to be required in ESRD patients undergoing hemodialysis.

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“…Our research group [7] developed a formula for quantitative prediction of the hemodialyzability of a drug from 4 factors: molecular weight (MW), PBR, Vd, and the fraction of unchanged drug excreted in urine (fe). This formula enabled simple prediction of removal rates by hemodialysis ( R = 0.75, p = 4.82e−4) but is applicable to only intravenous drugs because the dataset used to develop it included only intravenous drugs.…”

Section: Introductionmentioning

confidence: 99%

Improved Formula for Predicting Hemodialyzability of Intravenous and Oral Drugs

Murakami¹,

Narita²,

Urata³

et al. 2021

Blood Purif

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Background: The rate of drug removal by hemodialysis needs to be considered when designing drug dosage regimens for patients on hemodialysis. We previously developed a simplified equation to predict the removal rates of intravenously administered drugs by hemodialysis. Here, we addressed shortcomings of this equation and developed a more accurate equation that can also predict the removal rates of orally administered drugs. Methods: A total of 70 drugs with known pharmacokinetic and physical parameters and drug removal rates that were measured during hemodialysis in clinical cases were randomly assigned at a 4:1 ratio to a training data group or a test data group. A prediction equation was developed by performing stepwise multiple regression analyses using the training data (i.e., the removal rate by hemodialysis) as the objective variable and pharmacokinetic parameters as the explanatory variables. The equation was validated using the test data. Results: Multiple regression analyses revealed that molecular weight (MW), protein binding rate, and fraction excreted unchanged in urine relative to the volume of distribution (Vd) were independently correlated with the drug clearance rate (adjusted coefficient of determination, 0.83; p = 2.2e−16). The following equation was obtained: drug removal rate by hemodialysis (%) = −17.32 × [log (MW)] – 0.39 × [protein binding rate (%)] + 0.06 × [fraction excreted unchanged in urine (%)/Vd (L/kg)] + 83.34. Validation of the equation using the test data showed a very high correlation between predicted and measured reduction rate (R = 0.93, p = 1.87e−6). Mean error was −3.34 (95% confidence interval: −10.03, 3.35), mean absolute error was 9.59, and root mean square error was 16.48. Conclusion: The modified equation derived in this study using pharmacokinetic and physical parameters as variables precisely predicted the removal rates of both intravenous and oral drugs by hemodialysis.

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Simple Formula for Predicting Drug Removal Rates During Hemodialysis

Cited by 7 publications

References 21 publications

Oral tranexamic acid combined with low molecular weight heparin only during dialysis sessions successfully controlled chronic disseminated intravascular coagulation associated with aortic aneurysm and aortic dissection in a dialysis patient: a case report with literature review

Oral tranexamic acid combined with low molecular weight heparin only during dialysis sessions successfully controlled chronic disseminated intravascular coagulation associated with aortic aneurysm and aortic dissection in a dialysis patient: a case report with literature review

Ambrisentan use in a HIV-1 infected patient with end-stage renal disease and pulmonary hypertension: minimal removal by hemodialysis - a case report

Improved Formula for Predicting Hemodialyzability of Intravenous and Oral Drugs

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