Effect of water deprivation on absorption (oral, intramuscular) and disposition of ampicillin in sheep

Abstract

The effects of a 72 h water deprivation on the absorption--intramuscular (i.m.) and oral and disposition of ampicillin, inulin and para-aminohippuric acid (PAH) were investigated in six sheep. After intravenous (i.v.) administration of ampicillin sodium (10 mg/kg), the water deprivation decreased slightly the initial volume of distribution (0.082 +/- 0.033 vs. 0.055 +/- 0.030 l/kg) but not the steady state volume of distribution. The plasma clearance was significantly decreased (6.21 +/- 1.94 vs. 3.90 +/- 1.92 ml/min/kg) and the mean residence time (MRT) was increased from 22.25 +/- 4.91 to 33.36 +/- 8.16 min. After i.m. administration of ampicillin sodium (20 mg/kg), ampicillin concentrations were systematically higher after a 3-day period of water deprivation than during the control period but the muscular absorption rate was not modified. After oral administration of ampicillin trihydrate (1 g in toto) plasma concentrations were much lower and more persistent than after an i.m. administration and the systemic availability remained low whatever the hydration status. Influences of water deprivation on ampicillin disposition were linked to adaptation of renal function as assessed by inulin and PAH clearances. The therapeutic relevance of the results are discussed for a better definition of dosage regimens for sheep reared in arid environments.