Specific therapy of digoxin intoxication in dogs by hybrid kidney overexpressing multidrug resistance protein.
BACKGROUND
We have recently developed a unique hybrid artificial kidney, where the proximal tubular cell line, over-expressing multidrug resistance protein, MDR-1 (PCTL-MDR), was cultured on hollow fibers. While this module efficiently removed digoxin in vitro, its efficacy in vivo remained to be determined.


METHODS
The system was scaled up by connecting 10 similar modules in parallel, with the MDR-1 (PCTL-MDR) overexpressed proximal tubular cell line cultured as in our previous study. The system was connected to dogs intoxicated with digoxin, a representative substrate of MDR-1. Blood was circulated for 90 minutes through the system. Arterial and venous blood concentrations of digoxin and inulin were monitored. Complete blood cell count and granulocyte elastase were measured before and at the end of the study.


RESULTS
By using the system with PCTL-MDR, the arterial digoxin concentration was dramatically decreased from 2.89 +/- 0.10 to 0.92 +/- 0.11 ng/mL, but not by the system with PCTL alone. The clearance was 22.4 +/- 2.1 and 1.5 +/- 0.2 mL/min for the PCTL-MDR and PCTL equipment, respectively. Inulin was not transported in either system. White blood cell and platelet counts were slightly reduced by the treatment while hematocrit was unchanged; the granulocyte elastase concentration was slightly increased.


CONCLUSIONS
These data suggest that our new type of hybrid kidney can selectively remove digoxin sufficiently to reduce its systemic blood concentration in dogs with digoxin intoxication. Taking previous studies into consideration, this system may be a more powerful tool for the treatment of intoxication.
Tsuruoka
Shuichi
S
Department of Clinical Pharmacology, Jichi Medical School, 3311 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. tsuru@jichi.ac.jp
Nishiki
Kenta
K
Sugimoto
Kohichi
K
Suzuki
Makoto
M
Imai
Masashi
M
Fujimura
Akio
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000506:poisoning*; D002460:Cell Line; D004077:Digoxin / Q000493:pharmacokinetics / Q000506:poisoning*; D004285:Dogs; D062787:Drug Overdose / Q000628:therapy; D015870:Gene Expression; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000502:physiology*; D007688:Kidneys, Artificial
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002316:Cardiotonic Agents; D004077:Digoxin