Comparative pharmacokinetics of intravenous cephalexin in pregnant, lactating, and nonpregnant, nonlactating goats.

The aims of this study were to describe and compare the pharmacokinetics of a single dose of cephalexin (10 mg/kg) after its intravenous (i.v.) administration to five goats in three different physiological status: nonpregnant nonlactating (NPNL), pregnant (P) and nonpregnant lactating (L). Blood samples were collected at predetermined times, and plasma concentrations of cephalexin were measured by microbiological assay. Relevant pharmacokinetic parameters were calculated using noncompartmental analysis. Statistical comparison was performed applying the nonparametric anova. No significant differences were found for cephalexin pharmacokinetic parameters between the L and the NPNL group. Median V(dss) was significantly lower in pregnant goats (0.09 [0.07-0.10] L/kg) compared with NPNL goats (0.16 [0.14-0.49] L/kg). Median total Cl and V(dz) were significantly lower in pregnant goats (0.25 [0.19-0.29] L/h·kg and 0.11 [0.10-0.13] L/kg, respectively) than in lactating goats (0.40 [0.32-0.57] L/h·kg and 0.20 [0.14-0.23] L/kg, respectively). Median AUC(0-∞) was significantly higher in pregnant goats (37.79 [34.75-52.10] µg·h/mL) than in lactating goats (25.11 [17.44-31.14] µg·h/mL). Our study showed that even though some pharmacokinetic parameters of cephalexin are altered in pregnant and lactating goats, these differences are unlikely to be of clinical importance; therefore, no dose adjustment would be necessary during pregnancy and lactation.

Ricobendazole kinetics and availability following subcutaneous administration of a novel injectable formulation to calves.

The plasma and abomasal fluid disposition kinetics of ricobendazole (RBZ) after subcutaneous (s.c.) administration of a novel injectable formulation to calves, and the comparative plasma availability after s.c. injection of RBZ and that obtained after oral treatment with albendazole (ABZ), were characterised. Six parasite-free Holstein calves received RBZ (solution 150 mg ml(-1)) by s.c. injection at 3.75 mg kg(-1) (Experiment 1). Experiment 2 was conducted in two experimental phases; in phase I, five calves (Group A) received RBZ by s.c. injection and five animals (Group B) were orally treated with ABZ (suspension 100 mg ml(-1)), at 5 mg kg(-1). Drug treatments were reversed for each group in phase II and given at 7.5 mg kg(-1). Samples of abomasal fluid (via cannula) and jugular blood were collected over 72 hours post-treatment and analysed by HPLC. RBZ and its sulphone metabolite were detected in plasma following its s.c. administration. RBZ was rapidly absorbed, reaching the plasma Cmax at 4.5 hours post-dosing. The sulphone metabolite followed a similar kinetic pattern. Both molecules were rapidly and extensively distributed into the abomasum, being detected in abomasal fluid between 30 minutes and 36 hours post-administration. An extensive plasma/abomasum exchange process, with ionic-trapping in the abomasum, accounted for the higher AUC value (>200 per cent) obtained for RBZ in abomasum compared with plasma. The s.c. treatment with RBZ formulated as a solution resulted in a significantly greater plasma availability (measured as ABZ sulphoxide) than the oral treatment with ABZ (suspension) given at the same dose rates.