Abstract
Intravenous, oral and intraportal doses of diperdipine were given to bile duct cannulated dogs in order to assess the impact of first pass effect on the pharmacokinetics of this compound. After intravenous and oral doses, absolute bioavailability was calculated to be 18.7%. Biliary excretion accounted for about 0.1% of the total clearance of diperdipine and did not contribute to the overall elimination of the drug. After intraportal administration, the bioavailable fraction of diperdipine was increasing up to 44.3% suggesting a prehepatic site of loss of the drug. This was also substantiated by the fact that after oral administration a lesser fraction was excreted in the bile, than after the intraportal dose. The drug was highly bound to plasma proteins (greater than 96%) and was largely distributed in the blood cells for which a concentration dependent process was observed.
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