Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485787 | Journal of Pharmaceutical Sciences | 2012 | 10 Pages |
Abstract
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 30Â mg were administered to six male pigs in a crossover design. Blood samples were collected at selected time-points up to 48Â h after dose. Relative to the IR formulation, the time to reach the maximum concentration (tmax) was delayed with the MR formulation from 1.3 to 8.7Â h with the 10Â mg dose and to 6.2Â h with the 30Â mg dose. The relative bioavailability (BA) was approximately 92% at 10Â mg and 79% at 30Â 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 10Â mg MR formulation in dogs showed a higher AUC CV of approximately 80%, a tmax 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.
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Authors
Rajesh Kulkarni, Nathan Yumibe, Zhongyi Wang, Xin Zhang, Cheng Cai Tang, Kenneth Ruterbories, Amy Cox, Robyn McCain, Gregory T. Knipp,