Groups of five pigs received intramuscular (i/m) doses of tiamulin base 11mg/kg and 22mg/kg bodyweight (equivalent to 13.6 and 27.2mg thf/kg bodyweight respectively) once daily for four consecutive days. (Trials by Anderson M.D. and others [?])
On the last day of medication the pigs were killed and the tissues harvested for microbiological assay. The results are shown in the following table.
| USA |
Anderson, M.D. and others (1994) |
Parenteral
dosage rate (thf)
equivalent |
Denagard® (tiamulin) activity (μg/g)
|
| Lung |
Tonsils |
Colon
mucosa |
Colon
contents |
| 13.6mg/kg |
26.9 |
3.23 |
2.58 |
3.09 |
| 27.2mg/kg |
71.0 |
8.44 |
8.99 |
24.9 |
|
A further study was conducted by McKellar, Q. A. and others (2004) to determine the plasma and target tissue distribution of Denagard injectable following a single i/m injection of 15mg tiamulin hydrogen fumarate per kg bodyweight.
Blood, lung tissue, colon wall and colon contents were collected and all samples stored at -20ºC until analysis.
The following parameters were determined:
| C max |
– mean maximum plasma concentration |
| AUC |
- area under plasma concentration time curve |
| T max |
- Time of C max |
| AUC |
- area under plasma concentration time curve |
| MRT |
- mean residence time (See table below) |
| UK |
McKellar, Q.A. and others (2004) |
| Pharmacokinetics of Denagard® (tiamulin) in tissues calculated from mean concentrations from each time of kill following single i/m injection of tiamulin |
| |
Plasma |
Colon
wall |
Colon
contents |
Lung |
| AUC (μg h/ml) |
12.82 |
64.51 |
314.23 |
231.52 |
| AUMC (μg h2/ml) |
252.02 |
1252.78 |
9013.0 |
3868.1 |
| MRT (h) |
19.66 |
19.42 |
28.68 |
16.71 |
| C max (μg/ml) |
0.61 |
2.27 |
12.75 |
9.60 |
| t max (h) |
4.00 |
6.00 |
24.00 |
4.00 |
|
The C max and AUC values were very much higher for colon wall, colon contents and lung, than for plasma.
The mean tiamulin plasma and tissue levels are depicted below.
| UK |
McKellar, Q.A. and others (2004) |
| Pharmacokinetics of Denagard® (tiamulin) in tissues calculated from mean concentrations from each time of kill following single i/m injection of tiamulin |
 |
The concentrations of tiamulin in the lung tissues were much higher than in plasma. The ratio of mean lung/plasma concentrations were between 15:1 and 19:1 from 2 to 4 hours post-injection and even larger at 24 hrs and 32 hrs post-injection.
Mean lung concentrations were quite constant at approx 8.0µg/ml between 2 and 8 hours post-injection and were still in excess of 3.0µg/ml at 32 hours post-injection.
This study demonstrated that tissue concentrations in target tissues such as lung, colon and colon contents, achieved with a single i/m injectable dose of 15mg thf/kg bodyweight, exceeded the MIC values for key respiratory and enteric pathogens e.g. M. hyopneumoniae, Actinobacillus pleuropneumoniae, Brachyspira hyodysenteriae, Brachyspira pilosicoli and Lawsonia intracellularis.
