Barusiban suppresses oxytocin-induced preterm labour in non-human primates

Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Reinheimer, Torsten M [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2007

Schlagwörter:	Fenoterol Uterine Contraction Uterine Activity Amniotic Cavity Atosiban

Anmerkung:	© Reinheimer; licensee BioMed Central Ltd. 2007

Übergeordnetes Werk:	Enthalten in: BMC pregnancy and childbirth - London : BioMed Central, 2001, 7(2007), Suppl 1 vom: 01. Juni
Übergeordnetes Werk:	volume:7 ; year:2007 ; number:Suppl 1 ; day:01 ; month:06

Links:	Volltext

DOI / URN:	10.1186/1471-2393-7-S1-S15

Katalog-ID:	SPR027562875

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520			\|a Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term.
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allfields	10.1186/1471-2393-7-S1-S15 doi (DE-627)SPR027562875 (SPR)1471-2393-7-S1-S15-e DE-627 ger DE-627 rakwb eng Reinheimer, Torsten M verfasserin aut Barusiban suppresses oxytocin-induced preterm labour in non-human primates 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Reinheimer; licensee BioMed Central Ltd. 2007 Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. Fenoterol (dpeaa)DE-He213 Uterine Contraction (dpeaa)DE-He213 Uterine Activity (dpeaa)DE-He213 Amniotic Cavity (dpeaa)DE-He213 Atosiban (dpeaa)DE-He213 Enthalten in BMC pregnancy and childbirth London : BioMed Central, 2001 7(2007), Suppl 1 vom: 01. Juni (DE-627)335489087 (DE-600)2059869-5 1471-2393 nnns volume:7 year:2007 number:Suppl 1 day:01 month:06 https://dx.doi.org/10.1186/1471-2393-7-S1-S15 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2007 Suppl 1 01 06
spelling	10.1186/1471-2393-7-S1-S15 doi (DE-627)SPR027562875 (SPR)1471-2393-7-S1-S15-e DE-627 ger DE-627 rakwb eng Reinheimer, Torsten M verfasserin aut Barusiban suppresses oxytocin-induced preterm labour in non-human primates 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Reinheimer; licensee BioMed Central Ltd. 2007 Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. Fenoterol (dpeaa)DE-He213 Uterine Contraction (dpeaa)DE-He213 Uterine Activity (dpeaa)DE-He213 Amniotic Cavity (dpeaa)DE-He213 Atosiban (dpeaa)DE-He213 Enthalten in BMC pregnancy and childbirth London : BioMed Central, 2001 7(2007), Suppl 1 vom: 01. Juni (DE-627)335489087 (DE-600)2059869-5 1471-2393 nnns volume:7 year:2007 number:Suppl 1 day:01 month:06 https://dx.doi.org/10.1186/1471-2393-7-S1-S15 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2007 Suppl 1 01 06
allfields_unstemmed	10.1186/1471-2393-7-S1-S15 doi (DE-627)SPR027562875 (SPR)1471-2393-7-S1-S15-e DE-627 ger DE-627 rakwb eng Reinheimer, Torsten M verfasserin aut Barusiban suppresses oxytocin-induced preterm labour in non-human primates 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Reinheimer; licensee BioMed Central Ltd. 2007 Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. Fenoterol (dpeaa)DE-He213 Uterine Contraction (dpeaa)DE-He213 Uterine Activity (dpeaa)DE-He213 Amniotic Cavity (dpeaa)DE-He213 Atosiban (dpeaa)DE-He213 Enthalten in BMC pregnancy and childbirth London : BioMed Central, 2001 7(2007), Suppl 1 vom: 01. Juni (DE-627)335489087 (DE-600)2059869-5 1471-2393 nnns volume:7 year:2007 number:Suppl 1 day:01 month:06 https://dx.doi.org/10.1186/1471-2393-7-S1-S15 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2007 Suppl 1 01 06
allfieldsGer	10.1186/1471-2393-7-S1-S15 doi (DE-627)SPR027562875 (SPR)1471-2393-7-S1-S15-e DE-627 ger DE-627 rakwb eng Reinheimer, Torsten M verfasserin aut Barusiban suppresses oxytocin-induced preterm labour in non-human primates 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Reinheimer; licensee BioMed Central Ltd. 2007 Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. Fenoterol (dpeaa)DE-He213 Uterine Contraction (dpeaa)DE-He213 Uterine Activity (dpeaa)DE-He213 Amniotic Cavity (dpeaa)DE-He213 Atosiban (dpeaa)DE-He213 Enthalten in BMC pregnancy and childbirth London : BioMed Central, 2001 7(2007), Suppl 1 vom: 01. Juni (DE-627)335489087 (DE-600)2059869-5 1471-2393 nnns volume:7 year:2007 number:Suppl 1 day:01 month:06 https://dx.doi.org/10.1186/1471-2393-7-S1-S15 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2007 Suppl 1 01 06
allfieldsSound	10.1186/1471-2393-7-S1-S15 doi (DE-627)SPR027562875 (SPR)1471-2393-7-S1-S15-e DE-627 ger DE-627 rakwb eng Reinheimer, Torsten M verfasserin aut Barusiban suppresses oxytocin-induced preterm labour in non-human primates 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Reinheimer; licensee BioMed Central Ltd. 2007 Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. Fenoterol (dpeaa)DE-He213 Uterine Contraction (dpeaa)DE-He213 Uterine Activity (dpeaa)DE-He213 Amniotic Cavity (dpeaa)DE-He213 Atosiban (dpeaa)DE-He213 Enthalten in BMC pregnancy and childbirth London : BioMed Central, 2001 7(2007), Suppl 1 vom: 01. Juni (DE-627)335489087 (DE-600)2059869-5 1471-2393 nnns volume:7 year:2007 number:Suppl 1 day:01 month:06 https://dx.doi.org/10.1186/1471-2393-7-S1-S15 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2007 Suppl 1 01 06
language	English
source	Enthalten in BMC pregnancy and childbirth 7(2007), Suppl 1 vom: 01. Juni volume:7 year:2007 number:Suppl 1 day:01 month:06
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topic_facet	Fenoterol Uterine Contraction Uterine Activity Amniotic Cavity Atosiban
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Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. 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author	Reinheimer, Torsten M
spellingShingle	Reinheimer, Torsten M misc Fenoterol misc Uterine Contraction misc Uterine Activity misc Amniotic Cavity misc Atosiban Barusiban suppresses oxytocin-induced preterm labour in non-human primates
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topic_title	Barusiban suppresses oxytocin-induced preterm labour in non-human primates Fenoterol (dpeaa)DE-He213 Uterine Contraction (dpeaa)DE-He213 Uterine Activity (dpeaa)DE-He213 Amniotic Cavity (dpeaa)DE-He213 Atosiban (dpeaa)DE-He213
topic	misc Fenoterol misc Uterine Contraction misc Uterine Activity misc Amniotic Cavity misc Atosiban
topic_unstemmed	misc Fenoterol misc Uterine Contraction misc Uterine Activity misc Amniotic Cavity misc Atosiban
topic_browse	misc Fenoterol misc Uterine Contraction misc Uterine Activity misc Amniotic Cavity misc Atosiban
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title	Barusiban suppresses oxytocin-induced preterm labour in non-human primates
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title_full	Barusiban suppresses oxytocin-induced preterm labour in non-human primates
author_sort	Reinheimer, Torsten M
journal	BMC pregnancy and childbirth
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author_browse	Reinheimer, Torsten M
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author-letter	Reinheimer, Torsten M
doi_str_mv	10.1186/1471-2393-7-S1-S15
title_sort	barusiban suppresses oxytocin-induced preterm labour in non-human primates
title_auth	Barusiban suppresses oxytocin-induced preterm labour in non-human primates
abstract	Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. © Reinheimer; licensee BioMed Central Ltd. 2007
abstractGer	Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. © Reinheimer; licensee BioMed Central Ltd. 2007
abstract_unstemmed	Background Preterm labour (PTL) is a major cause of neonatal mortality and morbidity, and oxytocin (OT) antagonists are potential tocolytics. Atosiban (TRACTOCILE) is a mixed vasopressin $ V_{1A} $/OT antagonist registered for acute treatment of PTL in Europe. Other off-label drugs have serious side effects. Barusiban is a selective OT antagonist which has reached clinical development. A monkey model with OT-induced PTL was developed to compare barusiban and atosiban. In addition, the feasibility for long-term treatment of PTL with barusiban was explored. Methods Conscious pregnant cynomolgus monkeys were monitored for intrauterine pressure (IUP). A sensor for IUP was implanted into the amniotic cavity, and biopotential sensors for electromyogram were attached to the uterus. For short-term experiments, individual low-dose OT infusions induced stable submaximal uterine contractions. Barusiban and atosiban were administered either as intravenous bolus or infusion at high or low doses. For long-term treatment, low-dose OT was infused daily for 3–6 hours to mimic PTL. In addition, continuous high-dose infusions of barusiban (150 μg $ kg^{-1} $ $ h^{-1} $) or fenoterol (3 μg $ kg^{-1} $ $ h^{-1} $) were administered. Results Contractions of 15–40 mmHg were induced with individual OT infusions at 5–90 mU $ kg^{-1} $ $ h^{-1} $, and no OT-related desensitization occurred. Correlation was demonstrated between electromyograms and IUP curves. Barusiban was well tolerated and its potency was 4 times higher than atosiban's. Barusiban and atosiban demonstrated >95% efficacy. However, barusiban's duration of action was >13 hours (atosiban's 1–3 hours) and reversible with high-dose OT in emergency situations. OT control and fenoterol-treated monkeys delivered preterm (ca. day 154) and showed an increase in overall IUP. Barusiban-treated animals delivered normally following end of treatment (ca. day 163). Conclusion The presented telemetry model provides an excellent method to evaluate PTL drug candidates. OT induced stable repetitive contractions and no desensitisation. Barusiban and atosiban demonstrated high efficacy and rapid onset of action. Barusiban, a selective OT antagonist has higher potency and prolonged duration of action than atosiban. Barusiban effectively suppressed IUP during daily OT-challenges, delayed labour, and prolonged monkeys' pregnancy till term. © Reinheimer; licensee BioMed Central Ltd. 2007
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title_short	Barusiban suppresses oxytocin-induced preterm labour in non-human primates
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