Fig 1.
Construction of hemodialysis system using rat.
The miniaturized dialyzer (A) and schematic diagram of the HD protocol (B) were shown. Miniature dialyzer contained PES membrane (113 cm2) and was gamma sterilized. The renal failure model rat was prepared by bilateral renal nephrectomy. Heparin (100 U/mL) was administered as an anticoagulant with 0.2 mL/h flow rate. Blood pump was AC-2120 PERISTA® BIO-MINIPUMP. Dialysate pumps were AC-2120 PERISTA® BIO-MINIPUMP (inflow side) and Ceramic pump VSP-2050 (outflow side).
Table 1.
Hemodialysis conditions of HD rats compared with clinical setting.
Fig 2.
Physiological parameters of each rat with or without HD.
The blood of each HD rat was corrected and BUN (A), Na+ (B), K+ (C), Cl- (D), Hct (E) and Hb (F) were measured. Hemodialysis timing was represented by the gray area. The value of BUN reached a plateau at 140 mg/dL, which is the measurement limit of the i-STAT® 1 Analyzer. ○: HD rat (n = 4–7), ●: non-HD rat (n = 3–4). Values are expressed as the mean ± SD. BUN: blood urea nitrogen, Na+: sodium, K+: potassium, Cl-: chloride, Hct: Hematocrit, Hb: Hemoglobin.
Table 2.
Dialysis efficiency by HD rats.
Fig 3.
Plasma concentration-time curve of drugs by HD.
The blood of each HD rat was corrected and concentration of drugs [AMK (A), AP (B), VCM (C), DRPM (D), VPA (E) and APAP (F)] was measured. Hemodialysis timing was represented by the gray area. ○: HD rat (n = 4–7), ●: non-HD rat (n = 3–4). Values are expressed as the mean ± SD. AMK: amikacin sulfate, AP: aprindine hydrochloride, VCM: vancomycin hydrochloride, DRPM: doripenem hydrate, VPA: sodium 2-propylvalerate (valproic acid sodium), APAP: acetaminophen.
Table 3.
Comparison of drug removal of various drugs between humans and in vivo rat model.
Table 4.
PBR and Vd of various drugs between humans and in vivo rat model.
Table 5.
Parameter of predictive equation for drug dialyzabilities in HD patients using single or multiple linear regression model.
Fig 4.
Relationship between drug removal rates in humans and HD rats adjusted by various drug characteristics.
Relationship between drug removal rates in humans and unadjusted HD rats (A), HD rats adjusted for PBRunbind (B), HD rats adjusted for Vd (C), HD rats adjusted for PBRunbind/Vd (D). Correlativity between drug removal rates in humans and HD rats adjusted by various drug characteristics was calculated by R software program. PBRunbind: protein unbinding rate, Vd: distribution volume.