PMID: 7058762Feb 18, 1982

Pharmacokinetics of diltiazem in selected animal species and human beings

The American Journal of Cardiology
R W PiephoR K Browne


The absorption, distribution and elimination of diltiazem hydrochloride in rodent and canine species are reviewed. The drug is well absorbed but undergoes first pass metabolism after oral administration. Diltiazem is extensively distributed, and 52 to 81 percent is bound to serum protein, depending on the species studied. Diltiazem is metabolized in the liver by several pathways; deacetylation, N-demethylation, and O-demethylation are the primary degradative steps. The metabolites are excreted in urine and feces, indicating that biliary excretion occurs. There is some evidence for enterohepatic cycling. Diltiazem is rapidly eliminated (t 1/2 = 2.24 hours) in beagle dogs, and the relatively short half-life appears to be a result of the high level of plasma clearance (46.1 +/- 4.8 ml/min/per kg body weight). A comparison of the plasma diltiazem clearance with hepatic blood flow in the dog indicates that the drug is eliminated at a rate dependent on hepatic blood flow.


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