roles of cytochrome P450 and P-glycoprotein in the pharmacokinetics of florfenicol in chickens

The effects of three selective oral inhibitors, fluvoxamine [FLU], ketoconazole [KET], and verapamil [VER], on the pharmacokinetics [PK] of florfenicol [FFC] were investigated in chickens. The chickens were administered orally with saline solution [SAL], FLU [60 mg/kg], KET [25 mg/kg], or VER [9 mg/kg] for 7 consecutive days. Florfenicol was given to the chickens at a single dose of 30 mg/kg orally. Blood samples were collected from each chicken at 0 to 12 h post-administration of FFC. The plasma concentration of FFC was analyzed by high-performance liquid chromatography [HPLC]. The AUC of FFC increased and the Cl[s] of FFC decreased with oral co-administration of KET in chickens, and the C[max] of FFC increased with VER. While the AUC, the Cl[s] and the C[max] of FFC were all invariable with FLU. These data suggested that CYP 3A played a key role in the PK of FFC in chickens, however, P-glycoprotein [P-gp] and CYP 1A did not. The results imply that the adverse drug-drug interaction may occur in the use of FFC if the co-administrated drugs are the substrates, inducers or inhibitors of CYP 3A or/and P-gp

Acute renal failure following the use of rosiglitazone in a chronic kidney disease patient

Drug-induced acute interstitial nephritis is a well-recognised and important reversible cause of acute renal failure. Peroxisome-proliferator activated receptor-gamma agonists, such as rosiglitazone, have been proven to be safe in chronic kidney disease patients. We describe a 65-year-old man with long-standing diabetes mellitus and hypertension, presenting with a five-day history of fluid overload and uraemic symptoms. There was no ingestion of analgesics, alternative medicine and other nephrotoxic drugs, the only new prescription being rosiglitazone, which was commenced during his last clinic follow-up two weeks prior to presentation. He required haemodialysis with minimal improvement in renal profile, despite cessation of the offending drug. Renal biopsy revealed findings consistent with acute interstitial nephritis. An episode of upper gastrointestinal bleeding with bleeding duodenal ulcer limited the use of steroids. He was treated with a course of mycophenolate mofetil which showed good gradual response and he remained stable with residual renal impairment.