Pharmacokinetics and tissue distribution of the new non-imidazole histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy) propyl]piperidine in rats

Abstract

1. The aim of this study was to evaluate pharmacokinetics and tissue distribution of novel histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine (compound DL76).

2. Following intravenous administration of DL76 at the dose of 3 mg/kg, pharmacokinetic parameters were calculated using non-compartmental analysis. The systemic serum clearance was 10.08 L/h/kg and the estimated blood clearance was 5.64 L/h/kg. The volume of distribution at steady state was 16.1 L/kg which was greater than total body water, terminal half-life and MRT equalled 1.41 h and 1.6 h, respectively. The two-compartment pharmacokinetic model with enterohepatic circulation was also successfully fitted to the experimental data.

3. After systemic administration, DL76 was rapidly distributed into all organs studied (liver, kidney, brain, and lung). The highest AUC of DL76 was observed in lungs followed by brain, where the exposure to the investigated compound expressed as AUC was almost 30 times higher than in serum.

4. Bioavailability, calculated based on the area-under-the-concentration–time curve extrapolated to infinity after intravenous and intragastric administration of the dose 3 mg/kg, equalled 60.9%.

• Antagonist
• DL76 compound
• histamine H3 receptor
• LC/MS/MS
• serum
• rats

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.