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Article ; Online: Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals.

Knych, H K / Steffey, E P / Casbeer, H C / Mitchell, M M

2015 Volume 47, Issue 5, Page(s) 592–598

Abstract: Reasons for performing study: Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use.: Objectives: To describe fentanyl plasma concentrations following an escalating ... ...

Abstract	Reasons for performing study: Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. Objectives: To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. Study design: Experimental. Methods: Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes. Results: Foals mostly appeared to be unaffected following 2 μg/kg bwt (1.09 ± 0.41 μg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 μg/kg bwt (3.07 ± 1.11 μg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 μg/l) and 16 μg/kg bwt (17.4 ± 5.67 μg/l). All foals were heavily sedated after 32 μg/kg bwt (34.5 ± 10.3 μg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half-life following administration of the final dose was 44.2 ± 9.85 min. Conclusions: Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow.
MeSH term(s)	Analgesics, Opioid/administration & dosage ; Analgesics, Opioid/pharmacokinetics ; Analgesics, Opioid/pharmacology ; Animals ; Behavior, Animal/drug effects ; Conscious Sedation/veterinary ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Fentanyl/administration & dosage ; Fentanyl/pharmacokinetics ; Fentanyl/pharmacology ; Half-Life ; Horses ; Injections, Intravenous ; Male
Chemical Substances	Analgesics, Opioid ; Fentanyl (UF599785JZ)
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	41606-x
ISSN	2042-3306 ; 0425-1644
ISSN (online)	2042-3306
ISSN	0425-1644
DOI	10.1111/evj.12318
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Article ; Online: Effects of age on the pharmacokinetics and selected pharmacodynamics of intravenously administered fentanyl in foals.

Knych, H K / Steffey, E P / Mitchell, M M / Casbeer, H C

Equine veterinary journal

2015 Volume 47, Issue 1, Page(s) 72–77

Abstract: Reasons for performing study: The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been ... ...

Abstract	Reasons for performing study: The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been described for young foals. Objectives: The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages. Study design: Experimental study in healthy foals. Methods: Fentanyl was administered i.v. (4 μg/kg bwt) to a group of 9 foals on 3 separate occasions at 6–8, 20–22 and 41–42 days of age. Blood samples were collected prior to administration and at multiple times until 24 h post administration. Blood samples were analysed for fentanyl concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed. Results: The average volume of distribution was 3.55, 1.53 and 1.82 l/kg bwt and clearance 50.2, 40.7 and 35.7 ml/min/kg bwt when foals were 6–8, 20–22 and 41–42 days of age, respectively. The elimination half-life was slightly prolonged (49.3 min) at 6–8 days relative to 20–22 and 41–42 days of age (25.8 and 33.7 min, respectively). The primary metabolite detected in blood samples was the same as for adult horses. While the onset and duration varied widely between foals, sedation was observed at all ages studied. Conclusions: Fentanyl appears to be consistently well tolerated following i.v. administration of 4 μg/kg bwt to foals ranging in age from 1 to 6 weeks. The results of this study support further study of fentanyl for clinical use in foals.
MeSH term(s)	Aging ; Analgesics, Opioid/blood ; Analgesics, Opioid/pharmacokinetics ; Animals ; Area Under Curve ; Female ; Fentanyl/blood ; Fentanyl/pharmacokinetics ; Half-Life ; Horses/blood ; Horses/metabolism ; Male
Chemical Substances	Analgesics, Opioid ; Fentanyl (UF599785JZ)
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	41606-x
ISSN	2042-3306 ; 0425-1644
ISSN (online)	2042-3306
ISSN	0425-1644
DOI	10.1111/evj.12364
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Article ; Online: Preliminary pharmacokinetics of morphine and its major metabolites following intravenous administration of four doses to horses.

Knych, H K / Steffey, E P / McKemie, D S

Journal of veterinary pharmacology and therapeutics

2014 Volume 37, Issue 4, Page(s) 374–381

Abstract: The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, ... ...

Abstract	The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5 mg/kg morphine. Blood samples were collected up to 72 h postdrug administration, analyzed using LC-MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half-life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1 h, respectively, following administration of the four different IV doses. The volume of distribution at steady-state and systemic clearance ranged from 6.95 to 15.8 L/kg and 28.3 to 35.7 mL · min/kg, respectively. The only metabolites identified in blood samples were the primary metabolites identified in other species, 3-morphine-glucuronide and 6-morphine-glucuronide. Muscle fasciculations were observed at 0.2 and 0.5 mg/kg and ataxia noted at 0.5 mg/kg. Gastrointestinal activity was decreased in all dose groups (for up to 8 h in 7/8 horses and 24 h in one horse). This study extends previous studies and is the first report describing the metabolites of morphine in the horse. Plasma concentrations of morphine-3-glucuronide, a metabolite with demonstrated neuro-excitatory activity in mice, far exceeded that of morphine-6-glucuronide. Further study is warranted to assess whether the high levels of the morphine-3-glucuronide contribute to the dose-dependent excitation observed at high morphine doses.
MeSH term(s)	Analgesics, Opioid/administration & dosage ; Analgesics, Opioid/blood ; Analgesics, Opioid/metabolism ; Analgesics, Opioid/pharmacokinetics ; Animals ; Dose-Response Relationship, Drug ; Female ; Horses/blood ; Injections, Intravenous ; Male ; Morphine/administration & dosage ; Morphine/blood ; Morphine/metabolism ; Morphine/pharmacokinetics ; Morphine Derivatives/blood ; Morphine Derivatives/metabolism
Chemical Substances	Analgesics, Opioid ; Morphine Derivatives ; morphine-6-glucuronide (64Y9KYM60R) ; Morphine (76I7G6D29C) ; morphine-3-glucuronide (O27Z9CH39A)
Language	English
Publishing date	2014-08
Publishing country	England
Document type	Journal Article
ZDB-ID	435216-6
ISSN	1365-2885 ; 0140-7783
ISSN (online)	1365-2885
ISSN	0140-7783
DOI	10.1111/jvp.12098
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Article ; Online: Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

Esteller-Vico, A / Liu, I K M / Vaughan, B / Steffey, E P / Brosnan, R J

Animal reproduction science

2016 Volume 164, Page(s) 57–63

Abstract: Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares ...

Abstract	Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised.
MeSH term(s)	Animals ; Estradiol/pharmacology ; Estrous Cycle ; Female ; Horses ; Hydrogen-Ion Concentration ; Infertility, Female/veterinary ; Uterus/blood supply
Chemical Substances	Estradiol (4TI98Z838E)
Language	English
Publishing date	2016-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	429674-6
ISSN	1873-2232 ; 0378-4320
ISSN (online)	1873-2232
ISSN	0378-4320
DOI	10.1016/j.anireprosci.2015.11.012
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Article ; Online: Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse.

Rezende, M L / Grimsrud, K N / Stanley, S D / Steffey, E P / Mama, K R

Journal of veterinary pharmacology and therapeutics

2015 Volume 38, Issue 1, Page(s) 15–23

Abstract: The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug ... ...

Abstract	The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half-life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration.
MeSH term(s)	Adrenergic alpha-2 Receptor Agonists/administration & dosage ; Adrenergic alpha-2 Receptor Agonists/pharmacokinetics ; Animals ; Area Under Curve ; Dexmedetomidine/administration & dosage ; Dexmedetomidine/pharmacokinetics ; Female ; Horses/blood ; Injections, Intravenous ; Male
Chemical Substances	Adrenergic alpha-2 Receptor Agonists ; Dexmedetomidine (67VB76HONO)
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	435216-6
ISSN	1365-2885 ; 0140-7783
ISSN (online)	1365-2885
ISSN	0140-7783
DOI	10.1111/jvp.12138
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Article ; Online: Effects of vascular elastosis on uterine blood flow and perfusion in anesthetized mares.

Esteller-Vico, A / Liu, I K M / Vaughan, B / Steffey, E P / Brosnan, R J

Theriogenology

2015 Volume 83, Issue 6, Page(s) 988–994

Abstract: In the uterus of the mare, data obtained using transrectal Doppler ultrasonography indicate that uterine blood flow (UBF) is dynamic and changes throughout the estrous cycle. Degenerative lesions in the uterus are associated with subfertility and ... ...

Abstract	In the uterus of the mare, data obtained using transrectal Doppler ultrasonography indicate that uterine blood flow (UBF) is dynamic and changes throughout the estrous cycle. Degenerative lesions in the uterus are associated with subfertility and infertility. Among these lesions, vascular elastosis has been reported in aged, multiparous, and infertile mares. Angiosis of the uterine vasculature could potentially compromise UBF. The objectives of this experiment are to determine levels of UBF and perfusion of reproductively healthy mares and compare them to levels of subfertile/infertile mares affected by uterine vascular elastosis. Twenty mares were classified on the basis of degree of vascular degeneration and stage of cycle. A fluorescent microsphere technique was used to measure reproductive organ perfusion, where microspheres were injected into the left ventricle of the heart and became trapped in capillary beds in proportion to blood flow and tissue perfusion. The reproductive tract was removed, sectioned, and the fluorescent intensity evaluated to measure blood flow and perfusion. Additionally, full-thickness samples of the uterine wall were examined postmortem to further assess the degree of vascular degeneration in all layers of uterine wall. The mean value of uterine perfusion for the control mares during estrus (n = 5) was higher (P < 0.01) than that during diestrus (n = 5); 17.6 and 11.9 mL/min/100g, respectively. For the subfertile/infertile mares, the mean value of tissue perfusion was not different (P > 0.05) during estrus (n = 5) and diestrus (n = 5); 5.9 and 7.2 mL/min/100g, respectively. Uterine perfusion in subfertile/infertile mares affected by elastosis was lower than that of control mares during both estrus (P < 0.01) and diestrus (P < 0.01). The differences in baseline levels of perfusion between the control and elastosis groups indicate that elastosis of the uterine vasculature is associated with decreased uterine perfusion during both phases of the estrous cycle. In the uterus, a compromise in UBF could have implications in endometrial glandular development, postbreeding endometritis, uterine clearance, development of the conceptus, and overall fertility.
MeSH term(s)	Animals ; Estrous Cycle/physiology ; Female ; Horses/physiology ; Infertility, Female/veterinary ; Ultrasonography, Doppler/methods ; Ultrasonography, Doppler/veterinary ; Uterus/blood supply
Language	English
Publishing date	2015-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2014.11.032
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Article: Preliminary pharmacokinetics of morphine and its major metabolites following intravenous administration of four doses to horses

Knych, H. K / Steffey, E. P / McKemie, D. S

Journal of veterinary pharmacology and therapeutics. 2014 Aug., v. 37, no. 4

2014

Abstract	The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5� mg/kg morphine. Blood samples were collected up to 72� h postdrug administration, analyzed using LC‐MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half‐life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1� h, respectively, following administration of the four different IV doses. The volume of distribution at steady‐state and systemic clearance ranged from 6.95 to 15.8� L/kg and 28.3 to 35.7� mL·min/kg, respectively. The only metabolites identified in blood samples were the primary metabolites identified in other species, 3‐morphine‐glucuronide and 6‐morphine‐glucuronide. Muscle fasciculations were observed at 0.2 and 0.5� mg/kg and ataxia noted at 0.5� mg/kg. Gastrointestinal activity was decreased in all dose groups (for up to 8� h in 7/8 horses and 24� h in one horse). This study extends previous studies and is the first report describing the metabolites of morphine in the horse. Plasma concentrations of morphine‐3‐glucuronide, a metabolite with demonstrated neuro‐excitatory activity in mice, far exceeded that of morphine‐6‐glucuronide. Further study is warranted to assess whether the high levels of the morphine‐3‐glucuronide contribute to the dose‐dependent excitation observed at high morphine doses.
Keywords	blood ; gastrointestinal system ; horses ; intravenous injection ; metabolites ; mice ; morphine ; pharmacokinetics
Language	English
Dates of publication	2014-08
Size	p. 374-381.
Publishing place	Blackwell Science
Document type	Article
ZDB-ID	435216-6
ISSN	0140-7783
ISSN	0140-7783
DOI	10.1111/jvp.12098
Database	NAL-Catalogue (AGRICOLA)

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Article: Isoflurane-sparing effect of fentanyl in swine. Relevance and importance.

Steffey, E P

Anesthesiology

1995 Volume 83, Issue 3, Page(s) 446–448

MeSH term(s)	Animals ; Fentanyl/pharmacology ; Isoflurane/pharmacokinetics ; Pulmonary Alveoli/metabolism ; Species Specificity ; Swine
Chemical Substances	Isoflurane (CYS9AKD70P) ; Fentanyl (UF599785JZ)
Language	English
Publishing date	1995-09
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	269-0
ISSN	0003-3022
ISSN	0003-3022
DOI	10.1097/00000542-199509000-00002
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Article: Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse

Rezende, M. L / Grimsrud, K. N / Stanley, S. D / Steffey, E. P / Mama, K. R

Journal of veterinary pharmacology and therapeutics. 2015 Feb., v. 38, no. 1

2015

Abstract	The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half‐life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration.
Keywords	adults ; analgesic effect ; blood ; blood glucose ; dexmedetomidine ; half life ; horses ; intravenous injection ; pharmacokinetics ; physiological response
Language	English
Dates of publication	2015-02
Size	p. 15-23.
Publishing place	Blackwell Scientific Publications
Document type	Article
ZDB-ID	435216-6
ISSN	0140-7783
ISSN	0140-7783
DOI	10.1111/jvp.12138
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Article ; Online: Pharmacokinetics and pharmacodynamics of three intravenous doses of yohimbine in the horse.

Dimaio Knych, H K / Steffey, E P / Stanley, S D

Journal of veterinary pharmacology and therapeutics

2011 Volume 34, Issue 4, Page(s) 359–366

Abstract: Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable ... ...

Abstract	Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered alone. Nine healthy adult horses received a single intravenous dose of 0.1, 0.2, and 0.4 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 24 h postdrug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS), and resulting data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentrations were 106.0 ± 28.9, 156.7 ± 34.3, and 223.0 ± 44.5 ng/mL for doses of 0.1, 0.2, and 0.4 mg/kg, respectively. Immediately following administration, two horses showed signs of sedation, one horse appeared excited, while the other six appeared behaviorally unaffected. Episodes of tachycardia were noted within minutes of administration for all horses at all doses; however, there was no correlation between behavioral responses and episodes of increased heart rate. Sixty-three percent of the horses (8, 6, and 4 of the 9 horses in the 0.1, 0.2, and 0.4 mg/kg dose groups, respectively) exhibited second-degree atrial-ventricular conduction blocks and bradycardia prior to drug administration that transiently improved or disappeared upon administration of yohimbine. Gastrointestinal sounds were transiently increased following all doses.
MeSH term(s)	Adrenergic alpha-2 Receptor Antagonists/blood ; Adrenergic alpha-2 Receptor Antagonists/pharmacokinetics ; Adrenergic alpha-2 Receptor Antagonists/pharmacology ; Animals ; Behavior, Animal/drug effects ; Blood Glucose/drug effects ; Blood Proteins/metabolism ; Consciousness/drug effects ; Dose-Response Relationship, Drug ; Female ; Gastrointestinal Motility/drug effects ; Heart Rate/drug effects ; Hematocrit/veterinary ; Horses/metabolism ; Injections, Intravenous/veterinary ; Male ; Stimulation, Chemical ; Tachycardia/chemically induced ; Tachycardia/veterinary ; Yohimbine/blood ; Yohimbine/pharmacokinetics ; Yohimbine/pharmacology
Chemical Substances	Adrenergic alpha-2 Receptor Antagonists ; Blood Glucose ; Blood Proteins ; Yohimbine (2Y49VWD90Q)
Language	English
Publishing date	2011-08
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	435216-6
ISSN	1365-2885 ; 0140-7783
ISSN (online)	1365-2885
ISSN	0140-7783
DOI	10.1111/j.1365-2885.2010.01234.x
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In stock of ZB MED Cologne/Königswinter

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