The Inside Story

How Pulmotil姞 works
The Inside Story
Mode of action
Pulmotil moves into
the respiratory tract
immune system cells.1
Pulmotil works in concert with
Pulmotil-loaded immune cells respond to bacterial invasion.
Trachea
Bacterial
pathogens
Bronchi
Bronchioles
*ˆ}ÊVœ˜ÃՓiÃÊ*Տ“œÌˆ°
Lung
Stomach
Pulmonary alveolar macrophage
*Տ“œÌˆÊ«>ÃÃiÃÊvÀœ“Ê}ÕÌÊ
̜ÊLœœ`ÃÌÀi>“Ê>˜`ʈ˜ÌœÊ̅iÊ
ÀiëˆÊÀ>̜ÀÞÊÌÀ>VÌʈ““Õ˜iÊ
ÃÞÃÌi“ÊViÃ°ÊÌÊVœ˜Vi˜ÌÀ>ÌiÃʈ˜Ê
̅iʘ>Ã>ÊÌÕÀLˆ˜>ÌiÃ]ÊÌÀ>V…i>Ê
“ÕVœÃ>Ê>˜`ʏ՘}Ê̈ÃÃÕi°
/…iʓ>VÀœ«…>}iÃÊ>Àiʏ>À}i]Ê
Ü>˜`iÀˆ˜}ʓœ˜œ˜ÕVi>ÀÊViÃÊÊ
̅>ÌʜÀˆ}ˆ˜>Ìiʈ˜Ê̅iÊ̈ÃÃÕiÃÊ
œvÊÛ>ÀˆœÕÃÊ«>ÀÌÃʜvÊ̅iÊLœ`Þ°Ê
*Տ“œÌˆÊVœ˜Vi˜ÊÌÀ>ÌiÃʈ˜Ê̅iÊ
ÞÜܓiÃʜvÊ̅iʓ>VÀœ«…>}i]Ê
ÀiÃՏ̈˜}ʈ˜Ê>Ê*Տ“œÌˆ‡œ>`i`]Ê
`ˆÃi>Ãi‡vˆ}…̈˜}ÊVi°
1
Alveoli
Epithelial
cells
ÊL>VÌiÀˆ>Ê«>̅œ}i˜Êi˜ÌiÀÃÊ̅iʏ՘}Ã]ÊÌÀ>Ûiˆ˜}Ê̅ÀœÕ}…ÊÌÀ>V…i>]ÊLÀœ˜V…ˆÊ>˜`Ê
LÀœ˜V…ˆœiÃÊ̜Ê>Ûiœˆ]Ê܅iÀiʈÌÊ>ÌÌ>V…iÃÊ̜Êi«ˆÌ…iˆ>ÊViÃ°
2
*Տ“œÌˆ‡œ>`i`ʓ>VÀœ«…>}iÃ]ʓœ˜œVÞÌiÃÊ>˜`ʘiÕÌÀœ«…ˆÃÊ
>ÀiÊ>ÌÌÀ>VÌi`ÊLÞÊ̅iÊL>VÌiÀˆ>Ê̅ÀœÕ}…ÊV…i“œÌ>݈ÃÊ>˜`Ê
“ˆ}À>ÌiÊ̜Ü>À`Ê̅iÊL>VÌiÀˆ>°
the immune system.1
3
6
ÃÊ«>ÀÌʜvÊ̅iʈ““Õ˜iÊÀi뜘Ãi]Ê̅iʓ>VÀœ«…>}iÊ
Ãi˜`ÃʜÕÌÊ«ÃiÕ`œ«œ`ˆ>Ê­>À“îÊ̜ÊÃÕÀÀœÕ˜`Ê̅iÊL>VÌiÀˆ>Ê
«>̅œ}i˜°
7…i˜ÊvՏÞʍœˆ˜i`]Ê̅iʏÞÜܓiÊ>˜`Ê̅iÊ«…>}œÃœ“iÊ
LiVœ“iʜ˜iÊi˜ÌˆÌÞÊV>i`Ê>Ê«…>}œÞÜܓi°Ê˜Ãˆ`i]Ê
*Տ“œÌˆÊVœ˜Ì>VÌÃÊ̅iÊL>VÌiÀˆ>Ê>˜`ʎˆÃʈ̰Ê*Տ“œÌˆÊ
ÃÕ««i“i˜ÌÃÊ̅iʅœÃÌÊ`ivi˜ÃiʓiV…>˜ˆÃ“]ʓ>Žˆ˜}Ê
˜iÕÌÀœ«…ˆÃʓœÀiÊivviV̈Ûi°ÊÃÊ̅iʓ>VÀœ«…>}iÃÊ
`i}i˜iÀ>Ìi]Ê*Տ“œÌˆÊÀii>ÃiÃÊvÀœ“Ê̅iʘiÕÌÀœ«…ˆÊÊ
>˜`ÊLiVœ“iÃÊ>Û>ˆ>LiÊvœÀÊÀiVÞVˆ˜}ÊLÞÊÃV>Ûi˜}ˆ˜}Ê
“>VÀœ«…>}ið
Pseudopod
4
Phagolysosome
Pulmotil concentrates in the macrophage
more than these antibiotics, in-vitro1,2
Ratio of concentration
inside vs. outside macrophage
Medication
Tilmicosin (Pulmotil)
Phagosome (engulfed bacteria)
7…i˜ÊVœ“«iÌiÞÊÃÕÀÀœÕ˜`i`ÊLÞÊ̅iÊ«ÃiÕ`œ«œ`ˆ>]Ê̅iÊ
L>VÌiÀˆ>ÊLiVœ“iÊi˜}Տvi`ÊLÞÊ̅iʓ>VÀœ«…>}iʈ˜Ê܅>ÌʈÃÊ
V>i`Ê>Ê«…>}œÃœ“i°
50-75
ÀÞ̅Àœ“ÞVˆ˜
21
ˆ˜Vœ“ÞVˆ˜
2
i˜Ì>“ˆVˆ˜
<1
iv>i݈˜
<1
*i˜ˆVˆˆ˜
<1
Pulmotil in-vitro minimum inhibitory
concentrations (MIC)
5
Lysosome
(containing Pulmotil)
Microorganism
MIC (μg/mL)
Actinobacillus pleuropneumoniae a
Pasteurella multocida
a
Mycoplasma hyopneumoniae aa
Escherichia coli
Phagosome
(engulfed bacteria)
˜Ãˆ`iÊ̅iʓ>VÀœ«…>}i]Ê̅iÊ*Տ“œÌˆ‡œ>`i`ʏÞÜܓiÊ
vÕÃiÃÊ܈̅Ê̅iÊ«…>}œÃœ“i°
aa
£È
8
ä°x
€È{
Salmonella choleraesuis aa
€È{
Streptococcus suis aaW
€È{
H. parasuis aaÎ
ÊÊaÊ
ä°£Óx‡Ó
V̈ۈÌÞÊ>}>ˆ˜ÃÌÊ̅iÃiʜÀ}>˜ˆÃ“Ãʅ>ÃÊLii˜Ê`i“œ˜ÃÌÀ>Ìi`ÊVˆ˜ˆV>Þ°
/…iÊVˆ˜ˆV>ÊÈ}˜ˆvˆV>˜ViʜvÊ̅iÃiÊin-vitroÊ`>Ì>ʅ>ÃʘœÌÊLii˜Ê`i“œ˜ÃÌÀ>Ìi`°
W
-ÌÀ>ˆ˜ÊÌÞ«iʘœÌÊ`iÌiÀ“ˆ˜i`°
aaÊ
Conclusions
Mode of action makes
Pulmotil more effective
UÊ Ê >Lii`ÊvœÀÊ̅iÊVœ˜ÌÀœÊœvÊÃ܈˜iÊÀiëˆÀ>̜ÀÞÊ`ˆÃi>ÃiÊ>ÃÜVˆ>Ìi`Ê܈̅ÊActinobacillus pleuropneumoniaeÊ>˜`ÊPasteurella
multocida
UÊ Ê
œ˜Vi˜ÌÀ>ÌiÃʈ˜Ê`ˆÃi>Ãi‡vˆ}…̈˜}ʓ>VÀœ«…>}i]ʓœ˜œVÞÌiÊ>˜`ʘiÕÌÀœ«…ˆÊViÃÊ«ÀiÃi˜Ìʈ˜Ê̅iÊÀiëˆÀ>̜ÀÞÊÌÀ>VÌ4
UÊ *
Ê Õ“œÌˆÊŽˆÃÊL>VÌiÀˆ>Ê«>̅œ}i˜ÃÊ>˜`]ÊLiV>ÕÃiʈÌÊVœ˜Vi˜ÌÀ>ÌiÃÊ܅iÀiÊL>VÌiÀˆ>Ê«>̅œ}i˜ÃÊV>ÕÃiÊ`ˆÃi>Ãi]Ê*Տ“œÌˆÊ
ÃÕ««i“i˜ÌÃʅœÃÌÊ`ivi˜ÃiʓiV…>˜ˆÃ“ÃÊvœÀÊ>ÊÌÀՏÞÊ«œÌi˜ÌÊL>VÌiÀˆ>‡vˆ}…̈˜}ÊvœÀViÊ>}>ˆ˜ÃÌÊ«˜iՓœ˜ˆ>
UÊ Ê˜‡ÛˆÌÀœÊ`>Ì>ÊÃÕ}}iÃÌÃÊ*Տ“œÌˆÊ…>ÃʘœÊ`iÌÀˆ“i˜Ì>ÊivviVÌÃʜ˜Ê“>VÀœ«…>}iÊ>V̈ۈÌÞ£]{
In-vivo studies confirm:
Pulmotil concentrates at the site of infection
UÊ *
Ê Õ“œÌˆÊˆÃÊ«ÀœÛi˜ÊivviV̈ÛiÊin vitroʈ˜ÊLœÌ…Ê
Ê>˜`ÊÃi˜ÃˆÌˆÛˆÌÞÊÌiÃÌÃ]Ê
LÕÌÊ̅iÃiÊÌiÃÌÃÊ`œ˜½ÌÊ}ˆÛiÊ>ÊÌÀÕiʈ˜`ˆV>̈œ˜ÊœvʅœÜʈÌÊܜÀŽÃÊin vivo
UÊ In-vivoÊÌiÃÌÃÊVœ˜vˆÀ“Ê*Տ“œÌˆÊVœ˜Vi˜ÌÀ>ÌiÃÊ̅ÀœÕ}…œÕÌÊ̅iÊÀiëˆÀ>̜ÀÞÊ
ÌÀ>VÌ]Ê܅iÀiÊL>VÌiÀˆ>Ê>VVՓՏ>Ìi{]x]È
Pulmotil levels in whole lung tissue5
Mean alveolar macrophage concentrations (μg/mL)
after feeding 363 g/ton Pulmotil for 10 days4
Number of pigs
Tilmicosin mean
Tilmicosin (SD)
{ÊL>ÀÀœÜÃ
ÈÊ}ˆÌÃ
/œÌ>
£ä°ÈÎ
£Î°ÓÇ
£Ó°ÓÓ
™°Îä
™°ä™
n°Çx
*Տ“œÌˆÊVœ˜Vi˜ÌÀ>ÌiÃʈ˜Ê>Ûiœ>Àʓ>VÀœ«…>}iÃʜvÊLœÌ…ÊL>ÀÀœÜÃÊ>˜`Ê}ˆÌð
3.0
181 g/ton
Lung tilmicosin (μg/g)
Pulmotil concentration within the lung
363 g/ton
2.5
Pulmotil concentrates throughout the respiratory tract
2.0
Mean tilmicosin level, 8 pigsÈ
1.5
1.0
0.5
Linear Regression
0.0
0
2
4
7
10
14
Days following initial dose
UÊ Ê Õ˜}ʏiÛiÃÊÜiÀiÊ>««ÀœÝˆ“>ÌiÞÊ£äÊ̈“iÃʅˆ}…iÀÊ̅>˜ÊÃiÀՓʏiÛiÃ°Ê
­-iÀՓʏiÛiÃÊÀ>˜}i`ÊvÀœ“Êä°£äÊ̜Êä°ÓÎʖ}É}°®
UÊ Ê՘}ʏiÛiÃʈ˜VÀi>Ãi`ÊÈ}˜ˆvˆV>˜ÌÞÊvÀœ“Ê`>ÞÃÊÓÊ̜Ê{Ê«œÃÌÊÌÀi>̓i˜ÌÊ
>˜`ÊÜiÀiʓ>ˆ˜Ì>ˆ˜i`ÊvÀœ“Ê`>ÞÃÊ{Ê̜ʣ{°
UÊ ˆ}…iÀʏiÛiÃÊÜiÀiÊÀi>V…i`Ê>ÌÊÎÈÎÊ}É̜˜ÊÛðʣn£Ê}É̜˜°
Pulmotil dosage
Use
181–363 grams/ton
For the control of swine respiratory disease
associated with Actinobacillus pleuropneumoniae
and Pasteurella multocida.
Feeds containing tilmicosin must be withdrawn 7 days
prior to slaughter.
The label contains complete use information, including
cautions and warnings. Always read, understand and
follow the label and use directions.
1
Ê Ê>ˆÃ]ʰÊ>˜`Ê
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“>VÀœ«…>}ið»Ê*ÀœV°Ê£Î̅Ê*6-Ê
œ˜}ÀiÃð
Ê ÊÕÌÌÃ]ʰÊՏÞÊ£™™{°Êº˜ÌÀ>ViÕ>ÀÊVœ˜Vi˜ÌÀ>̈œ˜ÃʜvÊ>˜ÌˆL>VÌiÀˆ>Ê>}i˜ÌÃÊ>˜`ÊÀi>Ìi`ÊVˆ˜ˆV>Êˆ“«ˆV>̈œ˜Ã°»Ê
ˆ˜ˆV>Ê*…>À“>VœŽˆ˜ïVð
Î
Ê Êi,œÃ>]ʰ]Ê6ii˜…Տâi˜]ʰÊiÌÊ>°ÊÓäää°Êº˜ÊۈÌÀœÊÃÕÃVi«ÌˆLˆˆÌÞʜvÊ«œÀVˆ˜iÊÀiëˆÀ>̜ÀÞÊ«>̅œ}i˜ÃÊ̜Ê̈“ˆVœÃˆ˜°»Ê
°Ê6ḭʈ>}˜°Ê˜ÛiÃ̰
4
Ê Ê/…œ“ܘ]Ê/]ÊÕVŽ]ʰÊiÌÊ>°Ê£™™Ç°Êº*…>À“>Vœœ}ÞÊ>˜`ÊÃ>viÌÞʜvÊ*Տ“œÌˆÊˆ˜ÊÃ܈˜i°»Ê>˜VœÊ-܈˜iÊ*À>V̈̈œ˜iÀÊ
/iV…˜ˆV>Ê-i“ˆ˜>À]Ê+ÕiLiV°Ê
x
Ê Ê>˜VœÊÌÀˆ>Ê/x
8™ÎäÓ°Ê>Ì>ʜ˜Êvˆi°
È
Ê Ê-̜ŽiÀ]ʰ]Ê*>ÀŽiÀ]Ê,°Ê>˜`Ê-«i˜ViÀ]Ê9°Ê£™™È°Êº/…iÊVœ˜Vi˜ÌÀ>̈œ˜ÊœvÊ̈“ˆVœÃˆ˜Êˆ˜Ê«ˆ}ÊÃiÀՓÊ>˜`ÊÀiëˆÀ>̜ÀÞÊ̈ÃÃÕiÊ
vœœÜˆ˜}ʜÀ>Ê>`“ˆ˜ˆÃÌÀ>̈œ˜Ê܈̅Ê*Տ“œÌˆÊۈ>Ê̅iÊvii`Ê>ÌÊ>ʏiÛiÊœvÊ{ääÊ}É̜˜°»Ê*ÀœV°Ê£{̅Ê*6-Ê
œ˜}ÀiÃðÊ
2
*Տ“œÌˆ姞ʈÃÊ>ÊÌÀ>`i“>ÀŽÊvœÀʏ>˜Vœ½ÃÊLÀ>˜`ʜvÊ̈“ˆVœÃˆ˜°
>˜Vœ姞]Ê*Տ“œÌˆ姞ÊÊ>˜`Ê̅iÊ`ˆ>}œ˜>ÊL>ÀÊ>ÀiÊÌÀ>`i“>ÀŽÃʜܘi`ʜÀʏˆVi˜Ãi`ÊLÞʏˆÊˆÞÊ>˜`Ê
œ“«>˜Þ]ʈ̽ÃÊ
ÃÕLÈ`ˆ>ÀˆiÃʜÀÊ>vvˆˆ>Ìið
䊚ÊÓä£{ʏ>˜VœÊ˜ˆ“>Êi>Ì…°ÊÊÀˆ}…ÌÃÊÀiÃiÀÛi`°
1--1**8ää£äx
Serum
Bronchial
alveolar lavage
cells
Tracheal
epithelium
Lung tissue
ä°£Ê–}ɓ
ǰ£™Ê–}ɓ
Ó°£™Ê–}É}
£°È™Ê–}É}
>VÀœ«…>}i]ÊÌÀ>V…i>Ê>˜`ʏ՘}Ê̈ÃÃÕiÊVœ˜Vi˜ÌÀ>̈œ˜ÃÊÜiÀiÊÃÕLÃÌ>˜Ìˆ>ÞÊ
…ˆ}…iÀÊ̅>˜ÊÃiÀՓʏiÛiÃ°
Conclusions
UÊ *
Ê Õ“œÌˆÊܜÀŽÃʈ˜ÊVœ˜ViÀÌÊ܈̅Ê̅iÊ«ˆ}½Ãʘ>ÌÕÀ>Êˆ““Õ˜iÊÃÞÃÌi“1
UÊ Ê*Տ“œÌˆÊVœ˜Vi˜ÌÀ>ÌiÃʘi>ÀÞÊ£äÊ̈“iÃʓœÀiʈ˜Ê̅iʏ՘}Ê̅>˜ÊÊ
ˆ˜Ê̅iÊÃiÀՓ]Êi˜ÃÕÀˆ˜}ʅˆ}…Ê“i`ˆV>̈œ˜ÊiÛiÃÊ܅iÀiÊL>VÌiÀˆ>Ê
>VVՓՏ>Ìix
UÊ Ê*Տ“œÌˆÊVœ˜Vi˜ÌÀ>ÌiÃʈ˜ÊÃ܈˜iÊ«…>}œVÞÌiÃÊ­>Ûiœ>Àʓ>VÀœ«…>}iÃ]Ê
˜iÕÌÀœ«…ˆÃÊ>˜`ʓœ˜œVÞÌiî]Ê̅iÊ«ˆ}½Ãʘ>ÌÕÀ>Ê`ˆÃi>Ãi‡vˆ}…̈˜}ÊViÃ4
UÊ Ê*Տ“œÌˆÊVœ˜Vi˜ÌÀ>ÌiÃÊ>Ìʅˆ}…ʏiÛiÃÊ̅ÀœÕ}…œÕÌÊ̅iÊÀiëˆÀ>̜ÀÞÊ
ÌÀ>VÌÊ̜ʅi«Ê«ˆ}ÃÊvˆ}…ÌʜvvÊÀiëˆÀ>̜ÀÞÊ«>̅œ}i˜ÃÈ
CAUTION:Êi`iÀ>Ê>Üʏˆ“ˆÌÃÊ̅ˆÃÊ`ÀÕ}Ê̜ÊÕÃiÊ՘`iÀÊ̅iÊ«ÀœviÃȜ˜>Ê
ÃÕ«iÀۈȜ˜ÊœvÊ>ʏˆVi˜Ãi`ÊÛiÌiÀˆ˜>Àˆ>˜°Ê˜ˆ“>Êvii`ÊLi>Àˆ˜}ʜÀÊ
Vœ˜Ì>ˆ˜ˆ˜}Ê Ì…ˆÃÊ ÛiÌiÀˆ˜>ÀÞÊ vii`Ê `ˆÀiV̈ÛiÊ `ÀÕ}Ê Ã…>Ê LiÊ vi`Ê ÌœÊ
>˜ˆ“>Ãʜ˜ÞÊLÞʜÀÊÕ«œ˜Ê>ʏ>ÜvՏÊÛiÌiÀˆ˜>ÀÞÊvii`Ê`ˆÀiV̈ÛiʈÃÃÕi`Ê
LÞÊ >Ê ˆVi˜Ãi`Ê ÛiÌiÀˆ˜>Àˆ>˜Ê ˆ˜Ê ̅iÊ VœÕÀÃiÊ œvÊ Ì…iÊ ÛiÌiÀˆ˜>Àˆ>˜½ÃÊ
«ÀœviÃȜ˜>Ê«À>V̈Vi°
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