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Pharmacokinetics of dexamethasone and its effect on adrenal gland function in the dog.

The pharmacokinetics of dexamethasone (DXM) was studied in a group of 5 dogs given DXM alcohol or DXM 21-isonicotinate (as a solution) IV or IM (1 mg/kg of body weight) and DXM 21-isonicotinate (as a suspension) IM (0.1 or 1 mg/kg). Plasma concentrations were determined, using a high-performance liquid chromatography method. After IV administration, the half time of elimination was similar (120 to 140 minutes) for both formulations. In addition, all other pharmacokinetic parameters were not significantly different, indicating that DXM 21-isonicotinate renders DXM almost totally available. After IM administration, absorption was rapid for both solutions with a peak plasma concentration at 30 to 40 minutes. Bioavailability was approximately 100% for DXM alcohol, but limited (40%) for DXM 21-isonicotinate. After IM administration of DXM 21-isonicotinate (as a suspension) at 2 dosage rates (0.1 or 1 mg/kg), DXM was not detected in the plasma, suggesting a long phase of absorption. Plasma hydrocortisone (cortisol) values were similar after IM and IV administrations of DXM alcohol and DXM 21-isonicotinate (as a solution); after a short increase lasting 15 minutes, plasma hydrocortisone values decreased and returned to base line after a delay of 24 to 48 hours. After IM administration of DXM 21-isonicotinate as a suspension, plasma hydrocortisone values decreased for up to 10 days after the low dosage rate (0.1 mg/kg) and 1 month after the higher dosage rate (1 mg/kg).