Serum Fentanyl Concentrations Research Articles

SERUM FENTANYL CONCENTRATIONS AND BEHAVIOR ASSOCIATED WITH TRANSDERMAL FENTANYL APPLICATION ON HEALTHY CORN SNAKES (PANTHEROPHIS GUTTATUS).

Snakes are common household pets and frequently managed in zoos. Geriatric snakes commonly develop osteoarthritis, leading to a declining quality of life that often results in euthanasia. Anecdotally, the application of transdermal fentanyl patches (TFP) appears to contribute to clinical improvement, including increased activity level, in osteoarthritic snakes presumed to be in pain. This study evaluated serum fentanyl concentrations over time and the effects of TFP on the normal behavior of healthy, captive, adult corn snakes (Pantherophis guttatus) using constant video monitoring. Serum fentanyl concentrations were evaluated over 4 wk during 12.5 µg/h TFP application, and the results demonstrated long-lasting (>4 wk) serum concentrations that were consistent with analgesic efficacy in mammalian species during TFP application. At 4 wk of TFP application, mean serum fentanyl concentrations were 11.5 ± 5.5 ng/ml. Snakes were videotaped for 1 wk prior to and 2 wk after 12.5 µg/h TFP application, and behavior was evaluated by an ethogram. Behavioral changes associated with TFP application included decreased mean time spent active, decreased mean number of climbs, and decreased mean number of water visits; feeding behavior was unchanged. Overall, these results suggest that TFP application may provide safe, clinically effective analgesia in healthy corn snakes for at least 4 wk without inducing deleterious side effects, and may therefore be appropriate analgesia for management of osteoarthritic snakes.

An Open-Label Study of the Pharmacokinetics and Tolerability of Once-a-Day Fentanyl Citrate Patch in Japanese Pediatric and Adolescent Patients with Cancer Pain

Transdermal fentanyl is not yet approved for pediatric and adolescent use in Japan. Serum fentanyl concentration and the safety and efficacy of once-a-day fentanyl citrate patch were investigated in pediatric and adolescent patients with cancer pain. In this open-label, uncontrolled study, cancer patients aged 2-19 years being treated with strong opioid analgesics were switched to fentanyl citrate patch for 2 weeks. Serum fentanyl concentration was measured at steady state, and severity of pain was evaluated. Eleven patients (four patients aged 2-5 years and seven patients aged 6-19 years) were enrolled. No patient received a dose exceeding 2 mg. Mean serum fentanyl concentrations after administration of 0.5 mg, 1 mg, and 2 mg were 144 pg/mL (n=4), 277pg/mL (n=3), and 2070pg/mL (n=4), respectively. All patients were included in the efficacy and safety analysis, but one patient was excluded from the pharmacokinetic analysis because blood was sampled on the day after blood transfusion. A subgroup analysis showed that the mean serum fentanyl concentration tended to be higher in pre-school patients (aged 2-5years) than in school-aged and adolescent patients (aged 6-19years) and than in reports of adult patients (aged 20years and above) who received the same dose. No respiratory adverse events were observed, and pain was well controlled. Fentanyl citrate patch tended to result in a higher serum fentanyl concentration in pre-school patients than in school-aged, adolescent, and adult patients who received the same dose. The patch provided adequate pain control, was well tolerated, and did not cause respiratory adverse events. JPRN-JapicCTI-183909.

A Novel Clinical Consideration to Conserve Parenteral Fentanyl During the COVID-19 Pandemic.

A Novel Clinical Consideration to Conserve Parenteral Fentanyl During the COVID-19 Pandemic.

Characterizing Fentanyl Variability Using Population Pharmacokinetics in Pediatric Burn Patients.

Opioids are essential first line analgesics for pain management after burn injury. Opioid dosing remains challenging in burn patients, particularly in children, due to the immense variability in efficacy between patients. Opioid pharmacokinetics are altered in burned children, increasing variability and obviating dosing regimens extrapolated from adult-data. The present study aimed to characterize variability in fentanyl pharmacokinetics and identify significant contributors to variability in children with ≥10% total body surface area burn requiring fentanyl during routine wound care. We recorded patient demographics and clinical data. Blood samples were collected following fentanyl administration for pharmacokinetics at time 0, 30, 60, 120, and 240 minutes on day of admission and repeated on days 3 and 7. Serum fentanyl concentrations were quantified using tandem liquid chromatography mass spectrometry. Population analysis was used to estimate pharmacokinetics parameters. Fourteen patients, 1.2-17 years, with burns from 10-50.5% were included in analysis. A two-compartment model with body weight as a covariate best described fentanyl pharmacokinetics for the overall population. The population clearance and intercompartmental clearance were 7.19 and 2.16 L/hour, respectively, and the volume of distribution for the central and peripheral compartments was 4.01 and 25.1 L, respectively. Individual patient parameter estimates had extensive variability. This study confirmed the high variability in pediatric burn patient fentanyl pharmacokinetics and demonstrates similarities and differences to other populations reported in literature. Further research is needed with a larger number of patients to extensively investigate the impact of burns, genetic polymorphisms, and other factors on fentanyl efficacy and patient outcomes.

Identification of Cytochrome P450 Polymorphisms in Burn Patients and Impact on Fentanyl Pharmacokinetics: A Pilot Study.

Pain management is critical for burn care. Unfortunately, interindividual variation in pharmacokinetics (PK) due to burn hypermetabolism and genetic polymorphisms can lead to treatment failures in this at-risk population. Analgesics may be affected by genetic polymorphisms affecting cytochrome P450 (CYP) drug metabolizing enzymes. Fentanyl is a common opiate primarily metabolized by CYP3A4 subtypes. Recent studies demonstrate CYP2D6 variants, affecting fentanyl PK. Functional CYP polymorphisms can significantly alter opiate levels resulting in inadequate analgesia or life-threatening toxicity. The goal of our study was to evaluate fentanyl PK and assess associations with CYP polymorphisms. We obtained samples from the previously banked blood of 13 patients (eight males and five females) with >20% TBSA burns. Mean (SD) patient age was 41.7 (14.5) years, and mean burn size was 25.8 (15.3) %TBSA. Plasma fentanyl was quantified, and CYP genotyping was performed. Pharmacokinetic analysis was performed using Monolix software (Lixsoft, France) with a two-compartment population model best-representing fentanyl profiles. Three CYP slow-metabolizing genotypes were identified, which included CYP2D6*9, CYP2D6*29, and CYP3A4*1B. All three patients with variant polymorphisms had increased serum fentanyl concentrations due to impaired clearance. This pilot study supports the need for further research in this topic, and CYP genotyping of individual patients prior to receiving opiate analgesics to inform precision-guided decisions, improve therapeutic efficacy, and, most importantly, increase patient well-being and safety.

Continuous infusion versus intermittent bolus doses of fentanyl for analgesia and sedation in neonates: an open-label randomised controlled trial

ObjectiveAdequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of...

Effects of Adrenaline on maternal and fetal fentanyl absorption in epidural analgesia: A randomized trial.

BackgroundThe combination of low‐dose local anesthesia and lipophilic opioids such as fentanyl is established as a standard solution for labor epidural analgesia. Fentanyl increases efficacy, but may have negative effects on the neonate in terms of reduced neonatal neurologic and adaptive capacity scores and breast feeding. We hypothesized that addition of adrenaline 2 μg/mL to a solution of bupivacaine 1 mg/mL and fentanyl 2 μg/mL would reduce the systemic uptake of fentanyl, resulting in reduced serum fentanyl in the fetus at birth.MethodsForty‐one nulliparous women requesting epidural analgesia were randomized to epidural analgesia with or without adrenaline. Blood samples were drawn from the mother with regular intervals, and at delivery. An umbilical vein blood sample (used as a proxy for fetal exposure) was drawn after clamping.ResultsThere were no significant differences between the groups in fentanyl concentrations in the umbilical vein and maternal serum at birth. There was a significantly lower mean area under the maternal serum‐concentration curve for the first 2 hours of treatment in the adrenaline group (mean difference 0.161 nmol h/L [0.034; 0.289], P = .015), implying slower systemic uptake in the adrenaline group initially. There were no significant differences in treatment duration, motor block, Apgar scores, umbilical pH and base excess, or mode of delivery.ConclusionsThe addition of adrenaline to an epidural solution containing fentanyl lowered maternal systemic serum fentanyl concentration during the first 2 hours, but did not lower serum fentanyl concentration in the umbilical vein and mother at delivery.

Bioequivalence and safety of a novel fentanyl transdermal matrix system compared with a transdermal reservoir system

Fentanyl is a potent synthetic opioid used for the management of chronic pain. A newer transdermal matrix system was developed and compared with a reservoir system used in the United States. An open-label, single-center, randomized, two-period crossover study was conducted to evaluate the bioequivalence of the transdermal matrix system to the transdermal reservoir system. Seventy-four subjects completed treatment with both the reservoir system (100 microg/h) and the matrix system (100 microg/h), each applied for 72 hours. After application of the first system, subjects completed a 9-day washout and then crossed over to receive the other system for another 72 hours. Blood samples for the determination of serum fentanyl concentrations were taken in each treatment period for up to 120 hours following application. The ratios of geometric means for maximum fentanyl concentration (Cmax) and area under the concentration-time curve (AUClast, and AUCinfinity) were 106 percent, 110 percent, and 110 percent, respectively. The 90% confidence intervals for the ratios of the geometric means were contained within the bioequivalence criteria of 80-125 percent. The matrix system adhered well to skin. Systemic and topical safety profiles were comparable between treatments. The transdermal fentanyl matrix system adhered well, was well tolerated, and produced systemic exposures of fentanyl that were bioequivalent to the reservoir system.

<b>日本人健康成人男性を対象としたフェンタニル1日用テープの麻薬拮抗薬非併用下における生物学的同等性試験 </b>

FENTANYL Tape for 1 Day ⌈MEIJI⌋ is a generic drug of OneDuro® Patch (Janssen Pharmaceutical K.K.) under development by Meiji Seika Pharma Co., Ltd. and Yutoku Pharmaceutical Ind. Co., Ltd. The generic drug contains the same active ingredient fentanyl at the same dose in the same dosage form (transdermal absorption) as the original drug. In this study, 32 healthy male Japanese adults were recruited as subjects. Each subject applied a FENTANYL Tape for 1 Day 0.84 mg ⌈MEIJI⌋ and a OneDuro® Patch 0.84 mg once in a crossover manner, without concomitant use of antinarcotic. Bioequivalence of these drugs was investigated by analyzing pharmacokinetic parameters (Cmax and AUC0→t) as primary endpoints calculated from serum fentanyl concentration profiles in all 32 subjects. The results confirmed bioequivalence of the two products. Secondary endpoints including pharmacokinetic parameters such as AUC0→∞, MRTt and kel also supported bioequivalence of the two products. When a FENTANYL Tape for 1 Day 0.84 mg ⌈MEIJI⌋ or a OneDuro® Patch 0.84 mg was applied once for 24 hours without concomitant use of antinarcotic, there were no adverse events such as cutaneous reactions at the application site.

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.

Long-term use of a once-a-day fentanyl citrate transdermal patch in lung cancer patients.

Transdermal fentanyl is widely administered as an analgesic therapy for cancer patients. Recently, a novel fentanyl citrate transdermal patch was developed in Japan, which is the first such patch that requires changing only once a day. The patch releases more stable serum fentanyl concentrations and results in less frequent adverse skin symptoms compared with the conventional 72-h transdermal fentanyl patch. A previous study has reported the short-term analgesic effects and safety of this transdermal patch. However, the long-term efficacy has yet to be determined. Therefore, the present study retrospectively investigated the adverse effects and outcomes of treatment with this product in 46 lung cancer patients. In total, 35 (76%) patients were able to continue the treatment until the end of the observation period, including 32 (69%) who succumbed to the disease and three (7%) who were transferred from Nagoya City University Hospital to a hospice. Of the 11 (24%) discontinued cases, six were changed to a course of injectable opioids for the palliation of terminal symptoms, including dyspnea. Adverse effects were observed in 11 (24%) cases, but discontinuation due to adverse effects occurred in only four cases. Therefore, the present study indicates that palliative treatment with the once-a-day fentanyl citrate transdermal patch is well-tolerated by lung cancer patients.

Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study

This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl. CYP3A4*22 and CYP3A5*3 polymorphisms were analysed in 620 cancer pain patients receiving transdermal fentanyl (12.5-700 μg/h) from the European Pharmacogenetic Opioid Study. Using stepwise linear regression, CYP3A4/5 genetic variability was examined in combination with patient factors relating to organ drug elimination function and ABCB1 genetics for their association with serum fentanyl and norfentanyl concentrations and metabolic ratio (MR) (norfentanyl : fentanyl). Delivery rate-adjusted serum fentanyl concentrations (0.0012-1.1 nmol/l/μg.h) and MRs (0.08-499) varied widely. Only 43% of variability in serum fentanyl concentrations was accounted for by delivery rate and less than 50% by CYP3A4/5 genotypes and clinical variables (delivery rate, sex, comedications, kidney disease, BMI, serum albumin). CYP3A4*22 and CYP3A5*3 variants, CYP3A inhibitors and variables relating to liver and kidney function (serum albumin, glomerular filtration rate, kidney disease, BMI) were associated with MR, but accounted for only 14% of variability. Serum fentanyl concentrations and MR vary considerably between cancer pain patients on transdermal fentanyl patches. CYP3A4*22 and CYP3A5*3 genotypes, and multiple clinical factors, combine to influence transdermal fentanyl pharmacokinetics, but accounted for only a small proportion of variability in this study. Identification of the remaining factors determining serum fentanyl concentrations, and their relationship to efficacy and adverse effects may aid in improving the safety and effectiveness of transdermal fentanyl.

The fentanyl concentration required for immobility under propofol anesthesia is reduced by pre-treatment with flurbiprofen axetil

We hypothesized that nonsteroidal anti-inflammatory drugs decrease the plasma fentanyl concentration required to produce immobility in 50% of patients in response to skin incision (Cp50incision) compared with placebo under target-controlled infusion (TCI) propofol anesthesia. Sixty-two unpremedicated patients scheduled to undergo gynecologic laparoscopy were randomly assigned to receive placebo (control group) or flurbiprofen axetil 1 mg·kg(-1) (flurbiprofen group) preoperatively. General anesthesia was induced with fentanyl and propofol, and intubation was performed after succinylcholine 1 mg·kg(-1). Propofol was administered via a target-controlled infusion (TCI) system (Diprifusor™) set at an effect-site concentration of 5 μg·mL(-1). Fentanyl was given by a TCI system using the STANPUMP software (Schafer model). The concentration for the first patient was set at 3 ng·mL(-1) and modified in each group according to the up-down method. Skin incision was performed after more than ten minutes equilibration time. Serum fentanyl concentration, bispectral index (BIS), and hemodynamic parameters were measured two minutes before and after skin incision. The Cp50incision of fentanyl was derived from the mean of the crossovers (i.e., the serum fentanyl concentrations of successive participants who responded and those who did not or vice versa). Ten and 11 independent crossover pairs were collected in the control and flurbiprofen groups, respectively, representing 42 of 62 enrolled patients. The mean (SD) fentanyl Cp50incision was less in the flurbiprofen group [0.84 (0.63) ng·mL(-1)] than in the control group [1.65 (1.15) ng·mL(-1)]; P = 0.007; however, there were no differences in BIS, blood pressure, or heart rate, between groups. Preoperative flurbiprofen axetil decreased the Cp50incision of fentanyl by 49% during propofol anesthesia without changing the BIS or hemodynamic variables.

Serum Concentration of Fentanyl During Conversion From Intravenous to Transdermal Administration to Patients With Chronic Cancer Pain

To the best of our knowledge, there have been no reports on the pharmacokinetics and pharmacodynamics during the conversion from continuous intravenous infusion (CII) to transdermal fentanyl administration. The primary objective of the present study was to clarify the pharmacokinetic characteristics during this conversion. A secondary objective was to identify an association between serum albumin and the absorption of fentanyl from the transdermal patch. A prospective study was conducted from February 2010 to August 2011 that enrolled 19 patients with chronic cancer pain. Patients were classified into 2 study groups according to body mass index and albumin level. All patients received the conversion from CII to transdermal fentanyl using a 2-step taper of CII over 6 hours. Comparisons of efficacy, toxicity, and serum fentanyl concentrations between study groups were analyzed at baseline, 3, 6, 9, 12, 15, 18, and 24 hours after initiation of the conversion. The dose-adjusted serum fentanyl concentrations for all patients were significantly decreased at 15 to 24 hours after conversion compared with baseline, although pain intensity and the number of rescue events remained stable during the conversion. The dose-adjusted serum fentanyl concentrations at 9 to 24 hours were significantly reduced in the low albumin group compared with the normal albumin group (P<0.05). Our study demonstrated that the dose-adjusted serum fentanyl concentrations remained relatively stable, and pain intensity and the number of rescue events remained stable during conversion. Hypoalbuminemia was strongly associated with poor absorption of transdermally administered fentanyl.

Quantification of Serum Fentanyl Concentrations From Umbilical Cord Blood During Ex-Utero Intrapartum Therapy

Quantification of Serum Fentanyl Concentrations From Umbilical Cord Blood During Ex-Utero Intrapartum Therapy

Inhaled Fentanyl Aerosol in Healthy Volunteers

Rapid delivery of potent opioid to the systemic circulation is an important feature for the effective treatment of acute and acute-on-chronic breakthrough pain. The delivery of different opioids by the pulmonary route has been inconsistent, usually resulting in low bioavailability of the drug. Staccato® Fentanyl for Inhalation is a handheld inhaler producing a single metered dose of aerosolized fentanyl during a single inspiration. The aerosol is of high purity (≥98%) at a particle size (1 to 3.5 microns) shown to be best for pulmonary absorption. We conducted the study in healthy volunteers in 2 stages. In the crossover stage, 10 subjects received IV fentanyl 25 µg and inhaled fentanyl 25 µg on separate occasions. The dose escalation stage was a multidose, randomized, double-blind, placebo-controlled, single-period dose escalation study of inhaled fentanyl (50 to 300 µg). Serial blood sampling was performed over an 8-hour period after drug administration to determine the pharmacokinetic profile, and serial pupillometry was performed as a measure of pharmacodynamic effect. In the crossover stage the pharmacokinetic profiles of the inhaled and IV fentanyl showed similar peak arterial concentrations and areas under the curve. The time to maximum concentration was slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds, respectively. In the dose escalation stage the administration of repeated doses resulted in predictable, dose-dependent serum concentrations. This study has demonstrated that the pharmacokinetic profile of single doses of inhaled fentanyl is comparable to IV administration.

Randomized 5-Treatment Crossover Study to Assess the Effects of External Heat on Serum Fentanyl Concentrations During Treatment With Transdermal Fentanyl Systems

This randomized, open-label, 5-treatment, 5-sequence crossover study was designed to evaluate the effects of a heating pad on serum fentanyl concentrations with reservoir and matrix transdermal fentanyl systems. Subjects were randomized to 1 of 5 treatment sequences, receiving 5 fentanyl treatments (1 per period) for 36 hours: 25 µg/h reservoir without heat, 25 µg/h reservoir with heat, 25 µg/h matrix without heat, 25 µg/h matrix with heat, and a 50 µg/h reservoir without heat. The 25 µg/h systems with heat had a heating pad applied from 0 to 10 and 26 to 36 hours post application. Washout periods between treatments were 5 to 14 days. Naltrexone was given to block the opioid effects of fentanyl. Study results indicate that external heat had a similar effect on both matrix and reservoir systems, with heat applied during the first 10 hours of treatment increasing fentanyl exposure by approximately 61% to 81% at 10 hours (observed serum concentration at 10 hours) and overall exposure (area under the curve from 0 to 10 hours) by approximately 120% to 184%, but had minimal effect from 26 to 36 hours. The increased exposure observed with heat in both 25 µg/h systems, between 0 and 10 hours, was higher than that obtained with the 50 µg/h reservoir system applied without heat.

Population Pharmacokinetics of Transdermal Fentanyl in Patients With Cancer-Related Pain

ABSTRACTDetermining the appropriate dose of transdermal fentanyl (TDF) for the alleviation of cancer pain requires determining the factors causing variations in serum fentanyl concentration after TDF treatment. The objective of this study was to identify these factors and incorporate them into a formula that can be used to predict serum fentanyl concentration after application of a TDF patch. Blood samples of cancer patients treated with a TDF patch for the alleviation of pain were collected at 24, 48, and 72 hours after application to evaluate population pharmacokinetics using the nonlinear mixed-effect model (NONMEM). Based upon this evaluation, Child-Pugh Score and use of a cytochrome P450 3A4 (CYP3A4) inducer were identified as the most significant factors in variations in serum fentanyl concentration and incorporated into the following Final Model formula: CLfenta (L/h) = 3.53 × (15 − Child-Pugh Score) × (1 + 1.38 × use or no use of CYP3A4 inducer). Bootstrap evaluation of the Final Model revealed a high convergence rate, suggesting that the model formula is a reliable and useful tool for determining TDF dose for the alleviation of cancer pain.

Quantification of Serum Fentanyl Concentrations from Umbilical Cord Blood During Ex Utero Intrapartum Therapy

Fetal IM injection of fentanyl is frequently performed during ex utero intrapartum therapy (EXIT procedure). We quantified the concentration of fentanyl in umbilical vein blood. Thirteen samples from 13 subjects were analyzed. Medians and ranges are reported as follows. Weight of the newborn at delivery was 3000 g (2020-3715 g). The dose of fentanyl was 60 μg (45-65 μg). The time between IM administration of fentanyl and collection of the sample was 37 minutes (5-86 minutes). Fentanyl was detected in all of the samples, with a median serum concentration of 14.0 ng/mL (4.3-64.0 ng/mL).

Evaluation of an osmotic pump for fentanyl administration in cats as a model for nondomestic felids

To evaluate the reliability of an SC implanted osmotic pump (OP) for fentanyl administration in cats and to compare serum concentrations of fentanyl delivered via an OP and a transdermal patch (TP). Animals-8 spayed female cats. In a crossover design, cats received fentanyl at 25 microg/h via a TP or an OP. All cats were anesthetized for the pump or patch placement (0 hours) and again when it was removed (96 hours). Venous blood samples were collected for measurement of serum fentanyl concentrations at 0, 6, 12, 24, 36, 48, 72, and 96 hours and at 24 and 48 hours after device removal. After a 3-week washout period, the experiment was repeated with each cat receiving the other treatment. Mean serum fentanyl concentrations at 24, 36, 72, and 96 hours were greater when the OP was used than when the TP was used. Mean residence time and half-life were greater when the TP was used. Fentanyl concentration changed significantly faster in initial and elimination phases when the OP was used. Marked interindividual variation in serum fentanyl concentrations was evident with both administration methods. No adverse effects were evident with either method. Use of the OP to administer fentanyl to cats resulted in a shorter initial lag phase to a therapeutic serum concentration, higher bioavailability, and faster elimination after removal, compared with use of a TP. These advantages, in addition to the inability of cats to remove the OP, may make OPs useful for fentanyl administration in nondomestic felids.