Dexamethasone decreases plasma levels of the prochiral fenbendazole and its chiral and achiral metabolites in sheep

• Published in: Xenobiotica 2003-07, Vol.33 (7), p.731-742
• Main Authors: Sánchez, S., Small, J., Jones, D. G., McKellar, Q. A.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Dexamethasone - administration & dosage; Dexamethasone - analogs & derivatives; Dexamethasone - chemistry; Drug Interactions; Female; Fenbendazole - administration & dosage; Fenbendazole - analogs & derivatives; Fenbendazole - blood; Fenbendazole - chemistry; Injections, Intramuscular; Isomerism; Medical sciences; Metabolic Clearance Rate; Pharmacology. Drug treatments; Sheep - metabolism
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/0049825031000089119

1. The effect of co-administration of either short- or long-acting formulations of DXM on hepatic function and the plasma pharmacokinetic behaviour of prochiral fenbendazole (FBZ) and its metabolites was evaluated in sheep. 2. Neither DXM treatment markedly affected any of the biochemical markers of hepatic function tested. In contrast, both formulations significantly modified the plasma pharmacokinetic behaviour of FBZ and its metabolites. 3. Plasma FBZ concentrations and the associated area under the time-concentration curves were significantly lower, although the plasma detection period was longer (72 versus 48 h) in the DXM pretreated animals compared with those given FBZ alone. 4. DXM also appeared to alter the pattern of FBZ absorption, possibly through effects on abomasal pH. The shape of the plasma concentration-time curves for oxfendazole (OFZ) and fenbendazole sulphone (FBZSO 2) were similar to FBZ, raising the possibility that DXM treatment may have altered the liver biotransformation of the parent drug. 5. The concentrations of the (+) chiral metabolite of OFZ were significantly lower in DXM pretreated animals compared with those given FBZ alone. The trend was similar for the (−) antipode, although the differences between DXM pretreated and non-pretreated animals were not statistically significant.