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Tiamulin by Injection – PK/PD Relationships with M. hyorhinis and M. hyopneumoniae

by 5m Editor
17 May 2011, at 12:00am

A report of a study into the pharmaocokinetic and pharmacodynamic relationship between tiamulin (Denagard) given by injection and Mycoplasma hyorhinis and M. hyopneumoniae, presented by M. Makhanon (Novartis (Thailand) Ltd), D.G.S. Burch (Octagon Services Ltd, UK) and U. Klein (Novartis Animal Health Inc, Switzerland) at the 5th Asian Pig Veterinary Society Congress in Pattaya, Thailand, in March 2011.

Introduction

Tiamulin by injection (Denagard® – Novartis AH Inc.) was shown to be particularly effective against Mycoplasma hyorhinis- (MHR) associated arthritis in young growing swine, causing a marked reduction in swollen joints (1). An in-vitro microbiological study (2) showed that the minimum inhibitory concentrations (MICs) of tiamulin against both MHR and M. hyopneumoniae (MHP) were very low.

It was the purpose of this paper to look at the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of tiamulin against mycoplasmal isolates from Thailand.

Materials and Methods

Pharmacodynamics

The MIC 50 and MIC 90 values for tiamulin against 20 recent Thai isolates of MHP and MHR were reported (2).

Table 1. Susceptibility of 20 recent Thai MHP and MHR isolates to tiamulin
Species MIC 50
(µg/ml)
MIC 90
(µg/ml)
MIC range
(µg/ml)
MHP 0.048 0.097 0.048-0.19
MHR 0.097 0.097 0.048-0.097

Pharmacokinetics

Tiamulin distributes well into joint fluid after intramuscular administration. The concentrations achieved in plasma and joint fluid following an injection of Denagard 20% at 15mg per kg bodyweight was described (3, 4 & 5). Peak concentrations (Cmax) of tiamulin in plasma were recorded as 0.61μg/ml (4) and that, on average, concentrations in joint fluid were approximately 40 per cent of plasma concentration (3 & 5) (Ref Figure 1).

Results and Discussion

The correlation between plasma and joint fluid concentrations with the MIC 90 of MHP and MHR at 0.097μg/ml are highlighted in Figure 1.


Figure 1. Correlation of tiamulin PK in plasma and joint fluid and PD (MIC 90) against MHP and MHR

There is a good PK correlation with tiamulin concentrations in plasma exceeding the tiamulin MIC 90 for MHP over a 24-hour period. The recommended treatment interval is three applications over three consecutive days. Tiamulin concentrations in joint fluid are somewhat lower, but appear to cover 21 hours of the 24 hour (87.5 per cent) dosing period at the MIC 90 concentration. Many bacteriostatic antibiotics, which exert a concentration-related effect on the ribosome and thereby inhibit protein production, demonstrate a post-antibiotic effect (PAE) inhibiting bacterial regrowth for several hours (6) after plasma or tissue concentrations decline. This is likely to be the case for tiamulin against MHR.

Denagard injection at 15mg per kg bodyweight correlates well with its indications for the treatment of both mycoplasmal pneumonia and arthritis.

References

  1. Talummuk et al. 2010. Proc. IPVS Congress, 2:1012.
  2. Thongkamkoon et al.. 2010. Proc. IPVS Congress, 2:638.
  3. McKellar et al. 1993. Leo Report
  4. McKellar et al. 2004. Proc. IPVS Congress, 2:622.
  5. Skov & Nielsen. 1988. Leo Reports
  6. Diarra et al. 1999. Int. J. of Antimicrob. Agents, 12:229-237


Further Reading

- Find out more information on mycoplasmal arthritis by clicking here.


May 2011