A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects

Br J Clin Pharmacol. 2009 Mar;67(3):288-98. doi: 10.1111/j.1365-2125.2008.03351.x.


Aims: To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg).

Methods: Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy.

Results: The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2.

Conclusions: Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / pharmacokinetics*
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Young Adult


  • Histamine H1 Antagonists