In vivo evaluation of drug dialyzability in a rat model of hemodialysis
| Autor: | Sumio Hirata, Junji Saruwatari, Hiroki Ito, Ryota Tanaka, Kazuaki Taguchi, Mika Mori, Masaki Fukunaga, Keishi Yamasaki, Masaki Otagiri, Yuki Narita, Toru Maruyama, Daisuke Kadowaki, Satomi Hagiwara, Hiroshi Watanabe |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Physiology medicine.medical_treatment 030232 urology & nephrology Nephrectomy chemistry.chemical_compound 0302 clinical medicine Blood Flow Medicine and Health Sciences Urea Membrane Technology media_common Flow Rate Multidisciplinary Organic Compounds Physics Classical Mechanics Body Fluids Separation Processes Chemistry Blood Pharmaceutical Preparations Nephrology Physical Sciences Models Animal Medicine Engineering and Technology Hemodialysis Anatomy medicine.drug Research Article Biotechnology Drug medicine.medical_specialty Catheters Metabolic Clearance Rate Science media_common.quotation_subject 030106 microbiology Rat model Urology Surgical and Invasive Medical Procedures Bioengineering Fluid Mechanics Research and Analysis Methods Continuum Mechanics Urinary System Procedures 03 medical and health sciences Pharmacokinetics In vivo Renal Dialysis Medical Dialysis medicine Animals Humans Rats Wistar Dialysis Creatinine Molecular Dialysis Surgical Excision business.industry Organic Chemistry Chemical Compounds Biology and Life Sciences Fluid Dynamics Creatine Rats Renal Elimination Membrane Dialysis chemistry Doripenem Medical Devices and Equipment business |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 6, p e0233925 (2020) |
| ISSN: | 1932-6203 |
| Popis: | It is important to calculate the drug removal by hemodialysis (HD) for drug dosing regimens in HD patients. However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r2 = 0.936; p < 0.001) compared to unadjusted (r2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug. |
| Databáze: | OpenAIRE |
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