Possible mechanism for the anemia induced by candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, in rats.
Candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, was administered orally to male F344/Jcl and Crj:CD (SD) rats at 1000 mg kg(-1) day(-1) for 1-28 days, and the possible mechanism for the anemia induced by TCV-116 was investigated. In the TCV-116 group, the erythrocyte count, hematocrit value and hemoglobin concentration were decreased by 7-8% as compared with the values in the control group after dosing for 28 days. The plasma and renal erythropoietin levels, the reticulocyte count in the peripheral blood and the erythroid cell count upon bone marrow examination were decreased on day 7, but there were no accompanying histopathological renal lesions. Renal blood flow was increased, and mean blood pressure was decreased after TCV-116. These results suggest that the primary cause of the anemia induced by TCV-116 treatment is the increase in renal blood flow followed by a decrease in erythropoietin production.
Naeshiro
I
I
Drug Safety Research Laboratories, Takeda Chemical Industries, Osaka, Japan. naeshiro_ichirou@takeda.co.jp
Sato
K
K
Chatani
F
F
Sato
S
S
D000740:Anemia / Q000139:chemically induced* / Q000473:pathology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D001713:Biphenyl Compounds / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D004906:Erythrocyte Count / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil