Pharmacokinetics of fentanyl citrate and norfentanyl in Holstein calves and effect of analytical performances on fentanyl parameter estimation

Abstract

This study describes the pharmacokinetics of intravenously administered (i.v.) fentanyl citrate, and its primary metabolite norfentanyl in Holstein calves. Eight calves (58.6 ± 2.2 kg), aged 3-4 weeks, were administered fentanyl citrate at a single dose of 5.0 μg/kg i.v. Blood samples were collected from 0 to 24 hr. Plasma (nor)fentanyl concentrations were determined using liquid chromatography with mass spectrometry and a lower limit of quantification (LLOQ) of 0.03 ng/ml. To explore the effect of analytical performance on fentanyl parameter estimation, the noncompartmental pharmacokinetic analysis was then repeated with a hypothetical LLOQ value of 0.05 ng/ml. Terminal elimination half-life was estimated at 12.7 and 3.6 hr for fentanyl and norfentanyl, respectively. For fentanyl, systemic clearance was estimated at 2.0 L hr kg , volume of distribution at steady-state was 24.8 L/kg and extraction ratio was 0.42. At a hypothetical LLOQ of 0.05 ng/ml fentanyl half-life, volume of distribution at steady-state and clearance were, respectively, of 3.0 hr, 8.8 L/kg and 3.4 L kg hr . Fentanyl citrate administered i.v. at 5.0 μg/kg can reach levels associated with analgesia in other species. Pharmacokinetic parameters should be interpreted with respect to LLOQ, as lower limits can influence estimated parameters, such as elimination half-life or systemic clearance and have significant impact on dosage regimen selection in clinical practice.

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

“…18 Although our results suggest some species-specific differences in the pharmacokinetics of ertapenem in sheep and humans, it is important to note that analytical method sensitivity can have a profound effect on pharmacokinetics, as recently illustrated in the comparative pharmacokinetics of fentanyl in large animal species. 25 The limit of quantification of our assay was 0.25 µg/mL, and in the human literature limits of quantitation of 0.125 µg/mL have been reported. 13 As noted for fentanyl concentrations in large animal species, when comparing pharmacokinetic parameters it is important to consider analytical sensitivity as a lower limit of quantification can lead to the reporting of a longer elimination half-life.…”

Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

“…This may extend the half-life from our study when comparing to the other studies. This has been noted for other drugs in calves, an example being the comparison of the pharmacokinetics of fentanyl in calves to studies with higher LLOQ in goats and alpacas (13).…”

“…Twenty-four hours prior to initiation of the study, the calves were restrained and an IV jugular catheter was aseptically placed, and 2 h prior to the study a second IV jugular catheter was placed as previously described (13). The skin was aseptically prepared utilizing four alternating scrubs of chlorhexidine surgical scrub and 70% isopropyl alcohol.…”

“…The global extraction ratio (E body ) was calculated as reported by Toutain and Bousquet-Melou (18), with: E body =Systemic clearance/Cardiac output First calculated for each individual calf, and then combined for a mean value. With the calf cardiac output calculated as previously reported (13,18) as follows:…”

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)…”