Comparative pharmacokinetics studies of immediate- and modified-release formulations of glipizide in pigs and dogs

J Pharm Sci. 2012 Nov;101(11):4327-36. doi: 10.1002/jps.23292. Epub 2012 Aug 16.


The utility of pigs as preclinical animals for pharmaceutical development was assessed by evaluating the pharmacokinetics and pharmacodynamics of glipizide (Glucotrol®) following oral administration of immediate-release (IR) and modified-release (MR) formulations. Doses of 10 and 30 mg were administered to six male pigs in a crossover design. Blood samples were collected at selected time-points up to 48 h after dose. Relative to the IR formulation, the time to reach the maximum concentration (t(max) ) was delayed with the MR formulation from 1.3 to 8.7 h with the 10 mg dose and to 6.2 h with the 30 mg dose. The relative bioavailability (BA) was approximately 92% at 10 mg and 79% at 30 mg dose. The area under the curve of the plasma concentration versus time curve (AUC) increased nearly proportionally with the dose. Interanimal coefficient of variation (CV) in AUC ranged from approximately 40% to 60%. Blood glucose results suggest that pigs demonstrate formulation-dependent response to glipizide. Compared with the pigs, the 10 mg MR formulation in dogs showed a higher AUC CV of approximately 80%, a t(max) of 5.5 h, and a lower relative BA of 18%. These data indicate that the MR formulation performed less consistently in dogs as compared with humans, whereas the porcine absorption kinetics and BA were consistent with published clinical data.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Availability
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dogs
  • Glipizide / pharmacokinetics*
  • Hypoglycemic Agents / pharmacokinetics*
  • Male
  • Swine


  • Delayed-Action Preparations
  • Hypoglycemic Agents
  • Glipizide