Pharmacokinetics of Ertapenem in Sheep (Ovis aries) with Experimentally Induced Urinary Tract Infection

Abstract

Sheep are commonly used as animal models for human biomedical research, but descriptions of their use for studying the pharmacokinetics of carbapenem antimicrobials, such as ertapenem, are unavailable. Ertapenem is a critical antimicrobial for human infections, and the description of the pharmacokinetics of this drug is of value for research using ovine as models for human diseases, such as urinary tract infections (UTI). There are currently no ovine models for comparative biomedical research of UTI. The objective of this study was to report the pharmacokinetics of ertapenem in sheep after single and multiple dosing. In addition, we explored the effects of an immunomodulatory drug (Zelnate) on the pharmacokinetics of ertapenem in sheep. Eight healthy ewes (weight, 64.4 ± 7.7 kg) were used in an ovine bacterial cystitis model of human cystitis with Pseudomonas aeruginosa. After disease confirmation, each ewe received 1 g of ertapenem intravenously once every 24 h for 5 administrations. Blood was collected intensively (14 samples) during 24 h after the first and last administration. After multiple-dose administration, the volume of distribution was 84.5 mL/kg, clearance was 116.3 mL/h/kg, T1/2(λz) was 1.1 h, and the extraction ratio was 0.02. No significant differences in pharmacokinetic parameters or time points were found between groups treated with the immunostimulant and controls or after the 1st or 5th administration of ertapenem. No accumulation was noted from previous administration. Our ovine pharmacokinetic findings can be used to evaluate therapeutic strategies for ertapenem use (varying drug dosing schedules and combinations with other antimicrobials or immune modulators) in the context of UTI.Sheep are commonly used as animal models for human biomedical research, but descriptions of their use for studying the pharmacokinetics of carbapenem antimicrobials, such as ertapenem, are unavailable. Ertapenem is a critical antimicrobial for human infections, and the description of the pharmacokinetics of this drug is of value for research using ovine as models for human diseases, such as urinary tract infections (UTI). There are currently no ovine models for comparative biomedical research of UTI. The objective of this study was to report the pharmacokinetics of ertapenem in sheep after single and multiple dosing. In addition, we explored the effects of an immunomodulatory drug (Zelnate) on the pharmacokinetics of ertapenem in sheep. Eight healthy ewes (weight, 64.4 ± 7.7 kg) were used in an ovine bacterial cystitis model of human cystitis with Pseudomonas aeruginosa. After disease confirmation, each ewe received 1 g of ertapenem intravenously once every 24 h for 5 administrations. Blood was collected intensively (14 samples) during 24 h after the first and last administration. After multiple-dose administration, the volume of distribution was 84.5 mL/kg, clearance was 116.3 mL/h/kg, T1/2 ( λ z) was 1.1 h, and the extraction ratio was 0.02. No significant differences in pharmacokinetic parameters or time points ...

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report

“…Before employment for the study all goats were deemed healthy based on physical examination by large animal veterinary specialist. All goats had an intravenous catheter aseptically placed into each jugular vein as previously reported, with one catheter designated for blood collection and another one utilized for drug administration ( 11 , 19 ). Pantoprazole was reconstituted to a 4 mg/mL concentration per label instruction.…”

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration

“…Before enrollment for the study, all goats were deemed healthy based on physical examination by a board-certified large animal veterinary specialist. Prior to intravenous administration, all goats had intravenous jugular catheters aseptically placed as previously reported, ( 13 ) with one catheter designated for blood collection and another designated for drug administration. Esomeprazole was reconstituted to a concentration of 8 mg/mL in the manufacturer's vial with 5 mL of 0.9% sodium chloride (Sodium Chloride Injection, USP).…”

Pharmacokinetic Parameters and Estimated Milk Withdrawal Intervals for Domestic Goats (Capra Aegagrus Hircus) After Administration of Single and Multiple Intravenous and Subcutaneous Doses of Flunixin Meglumine

“…For FLU, the extraction ratio (E body ) was calculated as previously described (22)(23)(24) with: E body = Systemic clearance/Cardiac output (1) First, we calculated for each individual doe, and then combined them for a mean value, with the doe cardiac output described by Toutain et al (22)…”