A Single-Dose Pharmacokinetic Study of Metronidazole Administered to Gottingen Minipigs (Sus scrofa) by Oral Gavage or Voluntary Oral Dosing

Oral gavage (OG) dosing can be stressful to pigs and is associated with the risk of complications. To evaluate a potential refinement, we compared the pharmacokinetics of a drug with a known aversive taste (metronidazole) administered orally to 6 Gottingen minipigs with voluntary cooperation of the animal (voluntary oral [VO]) to 6 Gottingen minipigs dosed by OG. Blood was collected predose and at 0.5, 1, 2, 4, 8, and 24 h postdose and analyzed for drug concentration. Pharmacokinetic parameters for metronidazole were calculated, including C max , T max , AUC (from 0 to 24 h), and the ratios of AUC and C max between 2 dosing methods (AUC OG/VO ratio and C max OG/VO ratio, respectively). The time required to dose (dosing interval) and animal and staff acceptance of the dosing procedures were also assessed. All animals were dosed successfully, but one animal in each group was noted to have dosing difficulty. Mean dosing interval for OG dosing was greater than for VO (2.6 ± 0.24 min SD compared with 1.6 ± 0.36 min, respectively). VO dosing required fewer handlers, appeared to be less stressful to the animals, and was reported to be more ergonomically favorable than OG dosing. There were no significant differences in exposure including C max , T max , and AUC between OG and VO dosing. The OG/VO ratio was 1.27 for AUC and 1.25 for C max . Both animals with difficulty during dosing had pharmacokinetically inconsistent concentration–time profiles when compared with all other animals. These apparent differences were within the expected variability seen in pharmacokinetic studies. VO dosing may be a potential refinement for a single-dose pharmacokinetic study of an aversive tasting test material to minipigs.