Pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats

Abstract

The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane-anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End-tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 μg/kg), alfentanil (100 μg/kg), or sufentanil (1 μg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration-time data. A 3-compartment model best fitted the concentration-time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady-state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo-SD (range)], and the terminal half-life (min) [median (range)] were 0.25 ± 0.04 (0.09-0.34), 2.18 ± 0.16 (1.79-2.83), 18.6 ± 5.0 (15-29.8), and 151 (115-211) for fentanyl; 0.10 ± 0.01 (0.07-0.14), 0.89 ± 0.16 (0.68-1.83), 11.6 ± 2.6 (9.2-15.8), and 144 (118-501) for alfentanil; and 0.06 ± 0.01 (0.04-0.10), 0.77 ± 0.07 (0.63-0.99), 17.6 ± 4.3 (13.9-24.3), and 54 (46-76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half-lives for fentanyl and alfentanil, longer than for sufentanil.

Phenylpiperidine opioid effects on isoflurane minimum alveolar concentration in cats

“…Published pharmacokinetic models (Pypendop et al., 2014) were used to determine infusion rates for target phenylpiperidine concentrations. Measured opioid concentrations were reasonably close to target values and remained stable over the course of an approximately 3 hr infusion period, thereby serving to validate the models.…”

“…Continuing isoflurane anesthesia, a syringe pump (PHD 2000; Harvard Apparatus) and target‐controlled infusion computer software (Rugloop I, Demed) were used with individual‐specific pharmacokinetic models to intravenously administer fentanyl citrate (Baxter), sufentanil citrate (Baxter), or alfentanil hydrochloride (Baxter) to target drug plasma concentrations of 60, 10, and 500 ng/ml, respectively. Distribution volumes and elimination rate constants used to achieve plasma concentrations for each opioid were previously modeled for each individual cat in this study during isoflurane anesthesia (Pypendop, Brosnan, Majewski‐Tiedeken, Stanley, & Ilkiw, 2014). Phenylpiperidine concentrations studied are approximately equipotent (Glass, Gan, Howell, & Ginsberg, 1997;Mather, 1983;Wilde et al., 2019) and are similar in potency to the highest effective remifentanil concentrations (Brosnan et al., 2009) and alfentanil concentrations (Ilkiw et al., 1997) previously reported in cats.…”

Pharmacokinetics of intravenous and transdermal fentanyl in alpacas

“…reported peak serum fentanyl concentrations at 12 hr, with peak concentrations of 0.3 ± 0.08 ng/ml (Grubb et al., ). Transdermal uptake is variable among species with horses reaching peak plasma concentrations between 8 and 12 hr after patch application (Maxwell et al., ) while other species such as dogs and cats reach peak plasma concentrations between 12 and 14 hr (Lee et al., ; Pypendop et al., ). Peak plasma concentrations were also highly variable with one alpaca having a peak plasma concentration of 3.0 ng/ml at 8 hr and five alpacas having peak plasma concentrations ranging between 0.89 and 1.2 ng/ml at 24 hr.…”

“…The pharmacokinetics of fentanyl have been described after i.v. administration in dogs (Kukanich & Allen, ; Sano et al., ), cats (Lee, Papich, & Hardie, ; Pypendop, Brosnan, Majewski‐Tiedeken, Stanley, & Ilkiw, ), horses (Maxwell, Thomasy, Slovis, & Kollias‐Baker, ; Sanchez, Robertson, Maxwell, Zientek, & Cole, ; Thomasy, Mama, Whitley, Steffey, & Stanley, ), goats (Carroll, Hooper, Boothe, Hartsfield, & Randoll, ), and sheep (Ahern, Soma, Rudy, Uboh, & Schaer, ). Plasma concentrations of 0.95 ng/ml of fentanyl are associated with analgesia in dogs (Robinson et al., ; Sano et al., ).…”

Effects of a single intravenous bolus of fentanyl on the minimum anesthetic concentration of isoflurane in chickens (Gallus gallus domesticus)

“…The offset of the fentanyl MAC-reducing effect was observed to be short in this study and may be caused Table 2 Mean values ± standard deviation for heart rate (HR), respiratory rate (f R ), end-tidal partial pressure of carbon dioxide (PE 0 CO 2 ), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures, cloacal temperature (T), blood gas variables and arterial electrolyte concentrations in seven spontaneously breathing chickens anesthetized with isoflurane at 1.0 MAC (T1.0MAC) and 0.8 MAC before (T0.8MAC) and for 30 minutes after intravenous administration of fentanyl (30 mg kg À1 ) by rapid distribution and/or metabolism. The volume of distribution at steady state (V ss ) has been reported to be large in dogs (6.16 L kg À1 ) and cats (2.18 L kg À1 ) (Kukanich & Allen 2014;Pypendop et al 2014), as would be expected from fentanyl's high lipid solubility, and suggests extensive distribution out of the central compartment. Although V ss of fentanyl has not been reported in birds, it is expected to be large.…”