Pharmacokinetics and metabolism of diltiazem following multiple doses: comparing normotensive rat vs. hypertensive rat models in vivo.
In order to identify a suitable rodent model for preclinical study of calcium antagonists, pharmacokinetics and metabolism of diltiazem (DTZ) were compared in normotensive SD and hypertensive SHR rat models following multiple doses (5 mg/kg twice daily for 5 doses). Plasma concentrations of DTZ and its major metabolites appeared to be higher in the SHR than the SD rats, although the differences did not reach statistical significance (p > 0.05). The preliminary results suggest metabolism profile of DTZ in the SHR may be closer to humans than the SD rats and may be more preferred in pre-clinical drug development studies for DTZ.
Pharmacokinetics & Metabolism Laboratory, College of Pharmacy & Department of Medicine, 5968 College Street, Dalhousie University, Halifax, Nova Scotia, Canada. Pollen.Yeung@Dal.Ca
Pollen K F
PK
Yeung
Angelita
A
Alcos
Jinglan
J
Tang
William L
WL
Casley
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007279:Injections, Subcutaneous; D008297:Male; D023421:Models, Animal; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002121:Calcium Channel Blockers; D004110:Diltiazem