Plasma fentanyl concentrations in awake cats and cats undergoing anesthesia and ovariohysterectomy using transdermal administration

Objective To measure the plasma fentanyl concentrations achieved over time with transdermal fentanyl patches in awake cats and cats undergoing anesthesia and ovariohysterectomy. Study design Randomized prospective experimental study. Animals Twenty‐four purpose‐bred cats. Methods Cats were randomly assigned to three groups for Part I of a larger concurrent study. Group P received only a 25 μg hour^?1 transdermal fentanyl patch. Group P/A received the patch and anesthesia. Group A received only anesthesia. After a minimum 1‐week washout period, the cats were randomly reassigned to two groups for Part II of the larger study. Group P/A/O received the patch, anesthesia and ovariohysterectomy. Group A/O received anesthesia and ovariohysterectomy. Patches were left in place for 72 hours and plasma samples were obtained for fentanyl analysis while the patches were in place, and for 8 hours after patch removal for cats in Group P, P/A, and P/A/O. Results The 25 μg hour^?1 transdermal fentanyl patches were well tolerated by the cats in this study (mean body weight of 3.0 kg) and no overt adverse effects were noted. Mean plasma fentanyl concentrations over time, mean plasma fentanyl concentrations at specific times (8, 25, 49, and 73 hours after patch placement), time to first detectable plasma fentanyl concentration, time to reach maximum plasma fentanyl concentration, maximum plasma fentanyl concentration, mean plasma fentanyl concentration from 8 to 73 hours, elimination half‐life, and total area under concentration (AUC) were not statistically different among the groups. Conclusions Halothane anesthesia and anesthesia/ovariohysterectomy did not significantly alter the plasma fentanyl concentrations achieved or pharmacokinetic parameters measured, when compared with awake cats. There was a high degree of individual variability observed both within and between groups of cats in parameters measured. Clinical significance The high degree of variability observed suggests that careful observation of cats with fentanyl patches in place is required to assess efficacy and any potential adverse effects. Anesthesia and anesthesia/ovariohysterectomy do not appear to alter plasma fentanyl concentrations achieved by placement of a 25 μg hour^?1 transdermal fentanyl patch when compared to cats not undergoing these procedures.     

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.     

Analgesic Effect of the Transdermal Fentanyl Patch During and After Feline Ovariohysterectomy

OBJECTIVE: To evaluate the efficacy of the transdermal fentanyl patch in relieving perioperative pain and stress associated with ovariohysterectomy in cats. STUDY DESIGN: Prospective laboratory trial. ANIMALS: Twenty-four female, purpose-bred cats. METHODS: Each cat was randomly assigned to groups 1-3. Group 1 received a 25-microg/h transdermal fentanyl patch only. Group 2 received the patch and anesthesia. Group 3 received anesthesia only. Patches were left in place for 72 hours. Rectal temperature, heart rate, respiratory rate, indirect blood pressure, blood glucose, serum cortisol concentration, plasma fentanyl concentration, pain score, and excitement/sedation score were monitored at prescribed intervals over an 81-hour period. Cats from groups 1-3 were reassigned to groups 4 and 5. Group 4 received the patch, anesthesia, and an ovariohysterectomy. Group 5 received anesthesia and an ovariohysterectomy only. The study period and monitored parameters were the same as for groups 1-3. RESULTS: Serum cortisol concentrations were significantly lower in group 4 than group 5 during the surgical and early postsurgical time periods. A similar effect was noted in blood glucose concentrations during the surgical period. Rectal temperature was significantly higher in group 2 when comparing all anesthetized groups during the early postsurgical period. Pain scores were significantly higher in groups 4 and 5 than in groups 2 and 3 during the early postsurgical period. There was no significant difference in pain scores between groups 4 and 5 during this period, however. CONCLUSIONS: The transdermal fentanyl patch affects biochemical markers of perioperative pain and stress associated with ovariohysterectomy in cats, attenuating rises in serum cortisol and blood glucose concentrations during the surgical and early postsurgical periods. CLINICAL RELEVANCE: The transdermal fentanyl patch is effective in alleviating perioperative pain and stress associated with ovariohysterectomy in cats as evidenced by attenuated rises in cortisol and blood glucose concentrations in cats that were operated on and treated with the patch.     

Transdermal fentanyl patches in small animals

Fentanyl citrate is a potent opioid that can be delivered by the transdermal route in cats and dogs. Publications regarding transdermal fentanyl patches were obtained and systematically reviewed. Seven studies in cats and seven studies in dogs met the criteria for inclusion in this review. Dogs achieved effective plasma concentrations approximately 24 hours after patch application. Cats achieved effective plasma concentrations 7 hours after patch application. In dogs, transdermal fentanyl produced analgesia for up to 72 hours, except for the immediate 0- to 6-hour postoperative period. In cats, transdermal fentanyl produced analgesia equivalent to intermittent butorphanol administration for up to 72 hours following patch application.     

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.     

Assessment of serum concentrations and sedative effects of fentanyl after transdermal administration at three dosages in healthy llamas

OBJECTIVE: To determine the serum concentrations and sedative effects of fentanyl after transdermal administration at 3 dosages in llamas. ANIMALS: 9 healthy adult female llamas (mean age, 8 +/- 3 years; mean weight, 150 +/- 18 kg). PROCEDURE: Llamas were allocated to 1 of 3 groups (3 llamas/group). Fentanyl patches (each providing transdermal delivery of 75 microg of fentanyl/h) were placed on shaved areas of the antebrachium of all llamas. In group 1, llamas were treated with 1 patch (anticipated fentanyl dosage, 75 microg/h). In group 2, llamas were treated with 2 patches (anticipated fentanyl dosage, 150 microg/h). In group 3, llamas were treated with 4 patches (anticipated fentanyl dosage, 300 microg/h). For each llama, the degree of sedation was assessed by use of a subjective scoring system and a blood sample was collected for determination of serum fentanyl concentration at 12, 24, 36, 48, 60, and 72 hours after patch placement. RESULTS: Following the placement of 4 patches, mean +/- SD serum fentanyl concentration in group 3 llamas reached 0.3 +/- 0.08 ng/mL within 12 hours. This concentration was sustained for 72 hours. In group 2, application of 2 patches provided inconsistent results; in group 1, application of 1 patch rarely provided measurable serum fentanyl concentrations. No llamas became sedated at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that application of four 75 microg/h fentanyl patches provides consistent, sustained serum fentanyl concentrations without sedation in llamas. However, the serum concentration of fentanyl that provides analgesia in llamas is not known.     

Effect of transdermally administered fentanyl on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine the effect of two doses of fentanyl, administered transdermally, on the minimum alveolar concentration (MAC) of isoflurane in cats. STUDY DESIGN: Prospective, randomized study. ANIMALS: Five healthy, spayed, female cats. METHODS: Each cat was studied thrice with at least 2 weeks between each study. In study 1, the baseline isoflurane MAC was determined in triplicate for each cat. In studies 2 and 3, isoflurane MAC was determined 24 hours after placement of either a 25 or 50 microg hour(-1) fentanyl patch. In each MAC study, cats were instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Twenty-four hours prior to studies 2 and 3, a catheter was placed and secured in the jugular vein and either a 25 or 50 microg hour(-1) fentanyl patch was placed in random order on the left thorax. Blood samples for plasma fentanyl determination were collected prior to patch placement and at regular intervals up to 144 hours. After determination of MAC in studies 2 and 3, naloxone was administered as a bolus dose (0.1 mg kg(-1)) followed by an infusion (1 mg kg(-1) hour(-1)) and MAC redetermined. RESULTS: The baseline isoflurane MAC was 1.51 +/- 0.21% (mean +/- SD). Fentanyl (25 and 50 micro g hour(-1)) administered transdermally significantly reduced MAC to 1.25 +/- 0.26 and 1.22 +/- 0.16%, respectively. These MAC reductions were not significantly different from each other. Isoflurane MAC determined during administration of fentanyl 25 micro g hour(-1) and naloxone (1.44 +/- 0.16%) and fentanyl 50 micro g hour(-1) and naloxone (1.51 +/- 0.19%) was not significantly different from baseline MAC (1.51 +/- 0.21%). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl patches are placed to provide long-lasting analgesia. In order to be effective postoperatively, fentanyl patches must be placed prior to surgery. Plasma fentanyl concentrations achieved intraoperatively decrease the need for potent inhalant anesthetics in cats.     

The post-operative analgesic effects of epidurally administered morphine and transdermal fentanyl patch after ovariohysterectomy in dogs

ObjectiveTo investigate the analgesic and side effects of epidural morphine or a fentanyl patch after ovariohysterectomy in dogs.Study designProspective, randomized clinical study.AnimalsTwenty female mongrel dogs undergoing ovariohysterectomy.MethodsThe dogs were allocated to one of two groups: epidural morphine or transdermal fentanyl patch. Anaesthesia was induced with propofol and maintained with isoflurane. Morphine (0.1 mg kg^?1) was administered epidurally in the epidural morphine group and a transdermal fentanyl patch was applied 24 hours before the operation in the fentanyl patch group.The heart rate, respiratory rate, body temperature, plasma cortisol concentration, and sedation and analgesia scores were recorded during the 24 hour post-operative period. Adverse effects such as vomiting, anorexia, skin reactions, urinary retention, and time to start licking the surgical site were also recorded. p < 0.05 was considered significant. Statistical analyses utilized anova for repeated measures, Friedman tests, Mann-Whitney U-tests and independent sample t-tests as relevant.ResultsPain scores were lower in the epidural group than in the fentanyl group at all post-operative times. The dogs in the epidural morphine group were calm and relaxed, whereas discomfort and vocalization were recorded in the fentanyl patch group. The sedation scores were higher in the fentanyl patch group throughout the 12 hour period. Salivation and anorexia lasted longer in the fentanyl patch group than in the epidural morphine group. Plasma cortisol concentrations were high in the early post-operative period in both groups. The fentanyl patch group had higher cortisol concentrations than the epidural morphine group. Slight erythema was recorded in two dogs when the patches were removed.Conclusion and clinical relevanceEpidurally administered morphine provided better analgesia and caused fewer adverse effects than the fentanyl patch after ovariohysterectomy in dogs.     

Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses--variability among horses and its clinical implications

The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. There was much individual variation, however. The initial delay ranged from 0 to 5.1 h (mean, 1.91+/-2.0 h), Tcmax ranged from 8.5 to 14.5 h (mean, 11.4+/-2.7 h) and Cmax ranged from 0.67 to 5.12 ng/mL (mean, 2.77+/-1.92 ng/mL). In two horses, the plasma fentanyl concentration failed to reach even 1 ng/mL, whereas in the other four horses it was >1 ng/mL for at least 40 h and for at least 72 h in two of these horses. No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (>or=1 ng/mL) in about one-third of horses.     

Evaluation of transdermal fentanyl patch attachment in dogs and analysis of residual fentanyl content following removal

Objective To investigate whether the method used to attach matrix‐type fentanyl patches influences the degree of skin attachment and the amount of active drug remaining in patches after use. Study design Prospective, randomised clinical study. Study population Fifteen adult dogs of mixed breeds. Methods Two equally sized matrix‐type fentanyl patches were attached to the dorsal third of the lateral thorax of fifteen dogs for 72 hours. The two patches were attached using different techniques: Method AD used an adhesive dressing in combination with a transparent film. Method TG used tissue adhesive applied to the edges of the patch. After 72 hours the patches were removed and the proportion of the patch attached at this time calculated. The residual content of the patches was analysed using a validated gas chromatography–mass spectrometery (GC–MS) analysis technique. Results After 72 hours of continuous attachment, the mean proportion of drug uptake for method AD was 17.2 (SD ± 11.1)% and for method TG this was 16.9 (SD ± 7.3)%. The median proportion of attachment for method AD was 100% and for method TG was 95.6%. Conclusions The method of attachment did not significantly influence the uptake of fentanyl from matrix‐type patches. The method of attachment resulted in a significant difference in the proportion of the patch attached 72 hours after placement, with method AD resulting in a greater median proportion of attachment than TG. Clinical relevance The method used to attach matrix‐type fentanyl patches to dogs should not interfere with drug uptake. The residual fentanyl content remaining in these patches after 72 hours of continuous application is significant and could lead to intoxication if ingested by humans.     

Comparison of Plasma Fentanyl Concentrations by Using Three Transdermal Fentanyl Patch Sizes in Dogs

Objective—To compare plasma fentanyl concentrations attained after the application of three transdermal fentanyl patch sizes (50, 75, and 100 μg/hour) in dogs. Design—Repeated Latin square controlled study. Animals—Six intact, mixed-breed adult dogs (2 males, 4 females) weighing 19.9 ± 3.4 kg. Methods—Each dog was randomly assigned to receive each of three treatments: 50 (P50), 75 (P75), or 100 (P100) μg/hour transdermal patches. Patches were left in place for 72 hours. Jugular venous blood was collected at 1,2, 4, 8, 12, 24, 36, 48, 60, and 72 hours after patch application and for 1, 2, 4, 8, and 12 hours after patch removal. Plasma fentanyl concentrations were measured using a radioimmunoassay technique. After a 96-hour washout period, each dog was moved to another treatment group and received a different patch size. Results—The following results were obtained (mean ± SD): average plasma fentanyl concentration from 24 to 72 hours, 0.7 ± 0.2 ng/mL (P50), 1.4 ± 0.5 ng/mL (P75), 1.2 ± 0.5 ng/mL (P100); the total area under the concentration versus time curve (0 hours to infinity), 46 ± 12.2 ng/h/mL (P50), 101.2 ± 41.4 ng/h/mL (P75), 80.4 ± 38.3 ng/h/mL (P100); and the apparent elimination half-life, 3.6 ± 1.2 hours (P50), 3.4 ± 2.7 hours (P75), and 2.5 ± 2.0 hours (P100). There was a high degree of variability in plasma fentanyl concentrations achieved. Plasma fentanyl concentrations declined rapidly after patch removal. Conclusions—The attainment of steady-state plasma concentrations takes up to 24 hours, and there is a great deal of variability in the final concentrations reached in different individuals. In this study, the 100 μg/hour patches did not provide statistically increased plasma concentrations when compared with the 50 μg/hour patches. Clinical Relevance—Because of the interindividual and intraindividual variation in plasma fentanyl concentrations, patches should be applied 24 hours before the anticipated time that analgesia will be required. Adequacy of analgesia and potentially deleterious side effects, such as sedation and respiratory depression, should be monitored while the patches are in place. Skin reactions may occur, and the patches should be removed if such skin irritation is seen. After the patch is removed, it is expected that analgesia will wane rapidly because of the brief elimination half-life.     

Comparison of transdermal fentanyl and intramuscular oxymorphone on post-operative behaviour after ovariohysterectomy in dogs

The effects of transdermal fentanyl and im oxymorphone on behavioural and physiological responses, after ovariohysterectomy in dogs, were investigated. The study involved three groups of 10 dogs: fentanyl/surgery (FS), oxymorphone/surgery (OS), fentanyl/control (FC). A transdermal fentanyl delivery system (50 μg hour⁻¹) (FS and FC) was applied 20 hours before surgery, or IM oxymorphone (Os) was administered. After ovariohysterectomy (FS and OS) or anaesthesia alone (FC), dogs were continuously videotaped for 24 hours and a standardised hourly interaction with a handler performed. The videotapes were analysed, and interactive and non-interactive behaviours evaluated. In addition, pain and sedation scores, pulse and respiratory rates, rectal temperature, arterial blood pressure, plasma cortisol and plasma fentanyl concentrations were measured. This study showed that transdermal fentanyl and IM oxymorphone (0·05 mg kg⁻¹) produced comparable analgesic effects over a 24 hour recording period. IM oxymorphone produced significantly more sedation and lower rectal temperatures than transdermal fentanyl. There were no significant differences between groups in respiratory and heart rates, and arterial blood pressures.     

The effect of transdermal delivery of fentanyl on activity in growing pigs

Recently, decreased activity levels have been observed in pigs treated postoperatively with transdermal delivery of fentanyl (TD-fentanyl) after isoflurane anaesthesia. Whether the change in behaviour is related to opioid-induced sedation or to insufficient pain relief remains to be investigated. This study was therefore undertaken to evaluate the effect of TD-fentanyl 50 microg h(-1) on the activity level with and without isoflurane anaesthesia. Eight pigs (25.4 +/- 5.2 kg) were submitted to a cross-over study and given two treatments; 1) fentanyl patch applied after 30 minutes of anaesthesia (treatment A/F) and 2) fentanyl patch without anaesthesia (treatment F). The pigs' behaviour was observed from a video recording instantaneously every 10 minutes for 24 h before treatments and up to 72 h after the patch attachment. Venous blood samples were taken 1, 6, 12, 24, 48 and 72 h after the patch application. The behaviour recordings showed that TD-fentanyl did not produce sedation in any pig. No differences were found between the two treatments in activity level, weight gain or serum fentanyl concentration. This concentration measured after 24 h was 0.27 +/- 0.11 ng ml(-1) and 0.47 +/- 0.40 ng ml(-1) in the A/F and F group, respectively. In conclusion, transdermal delivery of 50 microg h(-1) fentanyl did not cause inactivity in growing pigs. However, the large variations in serum fentanyl concentration indicate that drug absorption from transdermal patches is unpredictable and sometimes deficient.     

Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats

OBJECTIVE: To compare postoperative discomfort assessed by subjective pain score and plasma cortisol concentrations in cats undergoing onychectomy that received analgesia by use of transdermal fentanyl (TDF) patches or an i.m. injection of butorphanol. DESIGN: Randomized prospective clinical trial. ANIMALS: 22 client-owned cats weighing 2.2 to 5 kg (4.84 to 11 lb) undergoing onychectomy. PROCEDURE: Researchers were blinded to which cats received a TDF patch (25 microg/h) 18 to 24 hours prior to surgery or an i.m. injection of butorphanol (0.2 mg/kg (0.09 mg/lb]) at the time of sedation, immediately following extubation, and at 4-hour intervals thereafter for 12 hours. Clinical variables, plasma cortisol concentration, and pain scores were evaluated and recorded 24 hours prior to surgery, at extubation, and 2, 4, 8, 12, 24, 36, and 48 hours after surgery. RESULTS: The TDF group had a lower pain score than the butorphanol group only at 8 hours after surgery. Both groups had significantly lower mean plasma cortisol concentrations 0, 24, 36, and 48 hours after surgery, compared with mean plasma cortisol concentrations prior to surgery. No significant differences in appetite or response to handling the feet were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Our data did not reveal a difference in pain relief between administration of TDF and butorphanol. Plasma cortisol concentrations were not different between groups. Fentanyl appeared to provide equivalent analgesia to butorphanol in cats undergoing onychectomy. The primary advantage of using a TDF patch is that repeated injections are not required.     

Pharmacokinetics of fentanyl after intravenous and transdermal administration in goats.

OBJECTIVE: To evaluate disposition of fentanyl in goats after IV and transdermal administration. ANIMALS: 8 healthy 2-year-old goats weighing 31.8 to 53.6 kg (mean+/-SD, 40.4+/-7.5 kg). PROCEDURE: Each goat was given 2 treatments consisting of fentanyl administered IV (2.5 microg/kg of body weight) and via a transdermal patch (50 microg/h). There was a 2-month interval between treatments. Blood samples were collected at specified times and analyzed in duplicate to determine plasma fentanyl concentrations. Pharmacokinetic values were calculated, using a computerized modeling program. RESULTS: Administration of fentanyl was tolerated by all goats. Intravenous administration of fentanyl resulted in a transitory increase in rectal temperature that was not clinically important. Terminal elimination half-life after IV administration was 1.20+/-0.78 h, volume of distribution at steady state was 1.51+/-0.39 L/kg, and systemic clearance was 2.09+/-0.62 L/kg/h. Transdermal administration of fentanyl resulted in variable plasma concentrations, with peak plasma concentrations ranging from 1.12 to 16.69 ng/ml (mean+/-SD, 6.99+/-6.03 ng/ml) and time to peak concentration ranging from 8 to 18 hours (mean+/-SD, 13+/-4.5 hours). After removal of the transdermal patch, mean+/-SD terminal elimination half-life was 5.34+/-5.34 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fentanyl (2.5 microg/kg) in goats results in a relatively short half-life that will limit its use for management of pain. Transdermal administration of fentanyl (50 microg/h) in goats results in variable plasma concentrations that may exceed those anticipated on the basis of a theoretical delivery rate, but stable plasma concentrations of fentanyl may not be achieved.     

Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2+/-1.1 ng/mL (mean+/-SD) and a time to peak serum concentration of 26+/-13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P < .05), but lameness scores were not significantly different (P > .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.     

The effect of rectal temperature on perianesthetic serum concentrations of transdermally administered fentanyl in cats anesthetized with isoflurane

OBJECTIVES: To determine whether moderate hypothermia during 4 hours of anesthesia with isoflurane substantially affects serum concentrations of transdermally administered fentanyl in the perianesthetic period in cats. ANIMALS: 7 healthy mature cats. PROCEDURE: A fentanyl patch (25 microg/h) was applied to the shaved thorax 24 hours before induction of anesthesia. Anesthesia was induced at time 0. Each cat received 2 treatments in a random order. Treatments were isoflurane anesthesia with normothermia and isoflurane anesthesia with hypothermia. Cats were intubated, connected to a nonrebreathing circuit, and maintained at 1.3X minimum alveolar concentration for 4 hours. Cats in the hypothermia treatment groups were actively cooled to 35 degrees C following the induction of anesthesia. Serum fentanyl analysis was performed at -24, -12, 0, 1, 2, 3, 4, 4.5, 5, 6, 7, 8, 9, 10, 12, and 24 hours. RESULTS: Mean +/- SEM serum fentanyl concentration (SFC) for the hypothermia treatment group (0.598 +/- 0.3048 ng/mL) was significantly lower than the baseline concentration (1.834 +/- 0.6393 ng/mL) at 1 hour. This significant reduction persisted for the duration of anesthesia for the hypothermia treatment group. Serum fentanyl concentrations returned to baseline values within 1 hour of the end of anesthesia, regardless of body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothermia during inhalant anesthesia induced a significant reduction in SFC obtained with transdermal administration. The impact of this reduction in SFC on the contribution of transdermally administered fentanyl to any reduction in the need for inhalant anesthesia remains to be determined.     

Pharmacokinetics of lidocaine following the application of 5% lidocaine patches to cats

Lidocaine patches have been used to provide local analgesia in dogs and cats. We conducted this study to assess the systemic and local absorption of lidocaine from topical patches in cats. Eight 2-year-old cats received either intravenous lidocaine at 2 mg/kg or one 700 mg lidocaine patch placed on the lateral thorax for 72 h, in a cross-over randomized repeated measures design. Plasma was collected at specific times and the skin was biopsied at the time of patch removal for the quantitative analysis of lidocaine and its major metabolite, monoethylglycinexylidide (MEGX), by gas chromatography with mass spectrometry. Percent absorption time plots for systemic lidocaine appearance were constructed using the Loo-Riegelman method. Approximately, constant rate absorption was observed from 12-72 h after patch application at a mean +/- SD rate of 109 +/- 49 microg/kg/h, resulting in steady-state lidocaine plasma concentrations of 0.083 +/- 0.032 microg/mL and MEGX concentrations of 0.012 +/- 0.009 microg/mL. Overall bioavailability of transdermal lidocaine was 6.3 +/- 2.7%, and only 56 +/- 29% of the total lidocaine dose delivered by the patch reached systemic circulation. Skin lidocaine concentrations were much higher than plasma concentrations, at 211 +/- 113 microg/g in the thoracic skin beneath the patch and 2.2 +/- 0.6 microg/g in the contralateral thoracic skin without the patch. As both lidocaine and MEGX were recovered from contralateral skin, it is likely that lidocaine accumulated in the skin from low systemic concentrations of circulating lidocaine over the 72-h period of patch application. Plasma lidocaine concentrations remained well below systemically toxic concentrations, and no obvious clinical side effects were observed in any of the cats. The low systemic absorption rate coupled with high local lidocaine concentrations on the skin support the safe use of lidocaine patches in cats.     

Accidental prehension and suspected transmucosal or oral absorption of fentanyl from a transdermal patch in a dog

A 100-microg hour(-1) transdermal fentanyl patch was applied to a 29-kg, 6-year-old, intact male mixed breed dog to help manage postoperative pain after total ear canal ablation and lateral bulla osteotomy. Two days later, the dog was found extremely sedated, and the reservoir of the transdermal patch was open. It was suspected that the dog ingested the contents of the reservoir of the transdermal patch and absorbed the fentanyl across its oral mucosa or through the gastrointestinal tract resulting in an overdose. The patch was removed, blood was drawn to determine serum fentanyl levels, and the dog recovered without incident. This clinical case documents the potential for neurologic sequelae, and bradycardia when fentanyl patches are used in animals to relieve postoperative pain.     

The use of fentanyl-patch in dogs undergoing spinal surgery: plasma concentration and analgesic efficacy

Objectives of this study were to evaluate plasma concentrations and analgesic efficacy of fentanyl administered transdermically in dogs undergoing spinal surgery. At the end of the surgery and before awakening, a fentanyl-patch was applied and was maintained in situ for 72 h. Blood samples were taken before the application of the patch, at 2, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48, 60, and 72 h after application and then 2, 4, 6, 8, 10, and 12 h after its removal. Before each blood sampling, pain evaluation was carried out using the Glasgow pain score, appropriately modified. Plasma concentrations of fentanyl were determined using a specific immuno-enzymatic kit. In this study, the minimum analgesic plasma concentration (0.23 ng/mL) required to achieve analgesia in human and considered to apply also for dogs was reached in all animals. No animal showed pain in the range of 'intense pain'; in two cases, the level of the pain was slight or moderate. No undesired effects were found. Results suggest that the use of transdermic patches could represent a valid aid in pain therapy in small animals; in particular, it contributes to the postoperative well-being of patients undergoing major surgery.