title: Effects of mesocaval shunt on the pharmacokinetics of metronidazole in young rats.
abstract: Prophylactic and therapeutic management of portosystemic encephalopathies is based on protein restriction in the diet, and the use of lactulose and antibiotics such as metronidazole. These actions intend to reduce the main source of intestinal ammonia production and release into the systemic circulation. The aim of this study was to evaluate the medium-term effects of mesocaval shunt on the pharmacokinetics of metronidazole in rats with healthy livers. Male Lewis rats were divided into two groups. The first group was subjected to mesocaval shunt (MCS) and the other employed as a control. The following tests were carried out in both groups: metronidazole pharmacokinetics, determination of ALT, AST, albumin, urea and ammonium, liver weight and histomorphology. A loss in body and liver weight was registered in rats subjected to MCS. AST levels also increased compared to controls. Significant differences in almost all pharmacokinetic parameters were detected between MCS and control rats, especially in Kel, AUC and Cmax. Modifications in metronidazole pharmacokinetics and liver weight changes without microstructural modification secondary to MCS were found. We suggest that individual drug-monitoring and pharmacokinetic analysis must be carried out in metronidazole medicated patients with modifications in portal circulation with or with out macro or micro liver structural alterations.
authors.affiliation: Laboratory of Experimental Surgery, Instituto Nacional de Pediatria-SSA, Mexico, City, Mexico.
authors.forename: Beatriz E Perez
authors.initials: BE
authors.lastname: Guillé
authors.forename: Fernando Villegas
authors.initials: FV
authors.lastname: Alvarez
authors.forename: Alejandra R
authors.initials: AR
authors.lastname: Toledo López
authors.forename: Miguel A Jiménez
authors.initials: MA
authors.lastname: Bravo-Luna
authors.forename: Rosa E
authors.initials: RE
authors.lastname: Soriano-Rosales
authors.forename: Ismael
authors.initials: I
authors.lastname: Lares-Asseff
authors.forename: Gerardo
authors.initials: G
authors.lastname: Arrellin
authors.forename: Maria G Pérez
authors.initials: MG
authors.lastname: Guillé
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007813:Laparotomy; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics*; D011167:Portacaval Shunt, Surgical; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole