Pharmacokinetics of transdermal flunixin in sows

Cramer, Catie; Pairis‐Garcia, Monique D.; Bowman, Andrew S.; Moeller, S. J.; Zhang, Yuntao; Sidhu, Pritam K.; Magnin, Géraldine; Coetzee, Johann F.

doi:10.1111/jvp.12772

Cited by 9 publications

(14 citation statements)

References 16 publications

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“…However, there appears to be no additional research on TD administration of FM in piglets for comparison. The t max for TD administration achieved in this study is longer than previous research in sows (27). Absolute bioavailability quantifies the fraction of a drug that is absorbed and available to produce its systemic effect (34).…”

Section: Discussionmentioning

confidence: 79%

“…Previous researchers have evaluated the PK of FM after IV, IM, and PO in mature swine (21,22), while FM PK in piglets has been evaluated for the IV and IM route of administration (23)(24)(25)(26). Additional research for TD in mature swine has also been reported since the completion of this study (27). Although the PK of IV FM has been reported in piglets (24), the IV route was FIGURE 2 | Observations vs. predictions.…”

Section: Discussionmentioning

confidence: 99%

“…The blood collection time points and washout period for TD application in this study were acquired from PK research conducted in cattle (8). Transdermal FM produced systemic drug levels consistent with concentrations in sows (27). However, there appears to be no additional research on TD administration of FM in piglets for comparison.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets

et al. 2020

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Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2.2 mg/kg for IV and IM and 3.3 mg/kg for PO and TD route. Plasma was collected at twenty-seven time points from 0 to 9 days after FM administration and concentrations were determined using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Pharmacokinetic data were analyzed using noncompartmental analysis (NCA) methods and nonlinear mixed-effects (NLME). Initial plasma concentration for IV (C 0) 11,653 µg/L and mean peak plasma concentrations (C max) 6,543 µg/L (IM), 4,883 µg/L (PO), and 31.5 µg/L (TD) were measured. The time points of peak FM concentrations (t max) were estimated 30 min, 1 h, and 24 h for IM, PO, and TD, respectively. The bioavailability (F) of PO and IM FM was estimated at >99%, while the bioavailability of TD FM was estimated to be 7.8%. The reported C max of FM after IM and PO administration is consistent with therapeutic concentration ranges that mitigate pain in other species and adult pigs. However, the low estimated concentration of FM after TD dosing is not expected to mitigate pain in pre-wean piglets. The low F of TD FM suggests that expanding the surface area of application is unlikely to be sufficient to establish an effective TD dose for pain, while the high bioavailability for PO FM should allow for an effective dose regimen to be established.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets

et al. 2020

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“…Time to reach maximum plasma concentration ( t max ) in toads was 1 h, which is faster than dairy cattle, goats, and pigs [ 14 , 16 , 20 , 21 ]. Furthermore, it should be noted that the current study failed to observe the absorption phase as the first sampling time (1 h) yielded the highest mean concentration.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)

Scott

Louis

Balko

et al. 2020

Veterinary Medicine International

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Transdermal administration is an important method of pharmacologic drug therapy in amphibians, made possible by their unique skin physiology and permeability. Despite this, there are relatively few studies that investigate transdermal pharmacokinetics in amphibians. The objective of this study was to investigate the pharmacokinetics of transdermal flunixin meglumine applied topically to marine toads (Rhinella marina). Twenty-one adult marine toads were administered flunixin meglumine (3.3 mg/kg) topically on their dorsum and randomized (n = 7/group) to blood collection at two timepoints from the following: 1, 2, 4, 8, 12, and 24 hours (h), using a sparse sampling protocol. Plasma was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Samples were analyzed individually and reported as a mean of the samples at each timepoint. The mean peak plasma concentration was 6.31 µg/ml, area under the curve was 29.37 μg-h/mL, and elimination half-life was 2.79 h. No adverse effects were noted in any animals. A subset of 12 animals were euthanized at serial timepoints and necropsied. Histopathology of skin and major organs revealed one minimal superficial lesion in a single toad potentially attributable to flunixin meglumine administration; otherwise, no other treatment-related lesions were observed in 11 of 12 toads. A single topical dose of transdermal flunixin meglumine was rapidly absorbed in marine toads in the current study, and peak plasma concentrations exceeded therapeutic ranges established in cattle with no significant pathologic findings.

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“…It has been utilized with pharmacokinetic parameters assessed in numerous species [4][5][6][7][8][9][10][11][12][13][14][15][16]. Pharmacokinetic properties of FM have been described in smaller non-breeding aged swine with weights ranging from 20 kg to 40 kg [3,17,18], mature swine (152-168 kg) [19], and sows (187-259 kg) [20], but scant research findings exist on finishing-age swine (90-130 kg).…”

Section: Introductionmentioning

confidence: 99%

A study to assess the correlation between plasma, oral fluid and urine concentrations of flunixin meglumine with the tissue residue depletion profile in finishing-age swine

et al. 2020

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Background: Flunixin meglumine (FM) was investigated for the effectiveness of plasma, oral fluid, and urine concentrations to predict tissue residue depletion profiles in finishing-age swine, along with the potential for untreated pigs to acquire tissue residues following commingled housing with FM-treated pigs. Twenty pigs were housed in groups of three treated and one untreated control. Treated pigs received one 2.2 mg/kg dose of FM intramuscularly. Before treatment and at 1, 3, 6, 12, 24, 36, and 48 h (h) after treatment, plasma samples were taken. At 1, 4, 8, 12 and 16 days (d) post-treatment, necropsy and collection of plasma, urine, oral fluid, muscle, liver, kidney, and injection site samples took place. Analysis of flunixin concentrations using liquid chromatography/ tandem mass spectrometry was done. A published physiologically based pharmacokinetic (PBPK) model for flunixin in cattle was extrapolated to swine to simulate the measured data. Results: Plasma concentrations of flunixin were the highest at 1 h post-treatment, ranging from 1534 to 7040 ng/ mL, and were less than limit of quantification (LOQ) of 5 ng/mL in all samples on Day 4. Flunixin was detected in the liver and kidney only on Day 1, but was not found 4-16 d post-treatment. Flunixin was either not seen or found less than LOQ in the muscle, with the exception of one sample on Day 16 at a level close to LOQ. Flunixin was found in the urine of untreated pigs after commingled housing with FM-treated pigs. The PBPK model adequately correlated plasma, oral fluid and urine concentrations of flunixin with residue depletion profiles in liver, kidney, and muscle of finishing-age pigs, especially within 24 h after dosing.

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Pharmacokinetics of transdermal flunixin in sows

Cited by 9 publications

References 16 publications

Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets

Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets

Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)

A study to assess the correlation between plasma, oral fluid and urine concentrations of flunixin meglumine with the tissue residue depletion profile in finishing-age swine

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