Absence of a significant pharmacokinetic interaction between atorvastatin and fenofibrate: a randomized, crossover, study of a fixed-dose formulation in healthy Mexican subjects.

Several clinical trials have substantiated the efficacy of the co-administration of statins like atorvastatin (ATO) and fibrates. Without information currently available about the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the effect when both drugs were co-administered. The purpose of this study was to investigate the pharmacokinetic profile of tablets containing ATO 20 mg, or the combination of ATO 20 mg with fenofibrate (FNO) 160 mg administered to healthy Mexican volunteers. This was a randomized, two-period, two-sequence, crossover study; 36 eligible subjects aged between 20-50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for ATO as the reference and ATO and FNO as the test product for bioequivalence design. The estimation computed (90% confidence intervals) for ATO and FNO combination versus ATO for Cmax, AUC0-t and AUC0-∞, were 102,09, 125,95, and 120,97%, respectively. These results suggest that ATO and FNO have no relevant clinical-pharmacokinetic drug interaction.

Renal dysfunction as a consequence of acute liver damage by bile duct ligation in cirrhotic rats.

UNLABELLED: Renal failure is a common complication in patients with alcohol-induced cirrhosis who undergo a superimposed severe alcoholic hepatitis. AIM: Our aim was to evaluate renal dysfunction established as a consequence of acute liver damage (ALD) induced by bile duct ligation (BDL) in cirrhotic rats. Hepatic and renal functional assays were performed. RESULTS: Hyperbilirubinemia and increased alanine aminotransferase and aspartate aminotransferase (p<0.05) in rats with BDL were observed since the first day of bile obstruction in cirrhotic rats. Urinary volume and urinary sodium concentration showed a significant reduction (p<0.05) on days 3 and 5 after BDL. Plasma renin activity, plasma renin concentration, serum creatinine, and BUN values increased (p<0.05) from day 1 to day 7 after BDL. Glomerular filtration rate was substantially decreased from day 1 to day 7. Histological changes became apparent since day 3 after BDL in which glomeruli with mesangial hypercellularity took place in the absence of tubular necrosis; with portal inflammation and proliferation of biliar conduits. Results of the present work demonstrate that ALD induced by BDL in cirrhotic rats produces changes in renal function. In conclusion, this experimental model demonstrates that an ALD of variable etiology, either surgical or induced by CCl(4), can cause important damage that eventually results in renal function deterioration. This experimental model may be suitable, to study the physiopathology of this syndrome, as well as for the evaluation of different pharmacological therapies.