title: Voluntary Oral Administration of Losartan in Rats.
abstract: Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.
authors.affiliation: Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal. lucilia.diogo@fcm.unl.pt.
authors.forename: Lucília N
authors.initials: LN
authors.lastname: Diogo
authors.affiliation: Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Inês V
authors.initials: IV
authors.lastname: Faustino
authors.affiliation: Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal; Department of Physiology, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Afonso
authors.affiliation: Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Pereira
authors.affiliation: Chronic Diseases Research Center (CEDOC), NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Emília C
authors.initials: EC
authors.lastname: Monteiro
authors.affiliation: Department of Physiology, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000830:Animals, Laboratory; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D009754:Nuts; D051381:Rats; D017208:Rats, Wistar
chemical_list: D057911:Angiotensin Receptor Antagonists; D019808:Losartan