Long-term effects of mesocaval shunt on the pharmacokinetic parameters of metronidazole in lewis rats

Portacaval shunts are commonly used to prevent gastroesophageal variceal bleeding secondary to portal hypertension. Ammonia encephalopathy is a common complication and it’s management includes antibiotics such as metronidazole, neomycin and recently, rifaximin. Metronidazole is often used in this context but its pharm acokinetics may be altered in these patients. Compare the pharmacokinetic parameters of two groups of rats, one of them after one year of having undergone mesocaval shunt. A randomized, experimental, prospective study in twenty adult male Lewis rats divided into two groups. The first group underwent mesocaval shunt and the other was the control group. Analyses of the following parameters were performed in both groups: (1) Pharmacokinetics of metronidazole by high-performance liquid chromatography, (2) Transaminase levels and (3) Body and liver weight. Differences between the MCS group and the control group were found for the pharmacokinetic parameters: Cm ax (p = 0.004), Ka (p = 0.009), Ka tl/2 (p = 0.007), Vd (p = 0.01), AUC (p = 0.05) and tmax (p = 0.01) and in ALT levels (p = 0.03) and liver weight (p = 0.00). The results obtained in this experimental model during one year of mesocaval shunt led us to suggest that metronidazole dosage should be decreased, without altering the administration schedule, because the drug levels reached in the mesocaval shunt group caused the animals to behave as if they had been given higher doses.