SciELO - Scientific Electronic Library Online

vol.80 issue1Cardiovascular effects of lumbar epidural anaesthesia in isoflurane-anaesthetised pigs during surgical removal of the liverA serological survey of leptospirosis in cattle of rural communities in the province of KwaZulu-Natal, South Africa author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand



Related links

  • On index processCited by Google
  • On index processSimilars in Google


Journal of the South African Veterinary Association

On-line version ISSN 2224-9435
Print version ISSN 1019-9128

J. S. Afr. Vet. Assoc. vol.80 n.1 Pretoria  2009




Residue depletion of colistin in swine after intramuscular administration



S S Tang; L J Gong; J K He; X Jin; X L Xiao

Division of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, National Reference Laboratory for Veterinary Drug Residues, 2 Yuanmingyuan West Road, Haidian District, Beijing, 100193, People's Republic of China




A newly formulated colistin sulphate solution was prepared in a previous study as a potential agent for intramuscular injection and its effectiveness, toxicity and pharmacokinetics were investigated. In order to provide more information to establish scientific guidance for safe use of this preparation, its residue depletion in swine tissues following intramuscular administration was investigated in this experiment. Fifty healthy cross-bred piglets (13.3 ± 0.9 kg) were used in this study. Five animals were kept as untreated controls and the other 45 animals were intramuscularly injected with the colistin preparation at a dose of 2.5 mg/kg of body weight. From the treated piglets, 5 animals were randomly selected and sacrificed at different withdrawal times. Liver, kidney and muscle tissues were sampled to examine the colistin residue levels by microbiological assay. The results showed that the colistin residue in liver and muscle decreased quickly and could not be detected at 1 day after the final dosing. However, the residue depletion in the kidneys was much slower than that in other tissues and even a small quantity of drug could be detected at 14 days after withdrawal. Using the method recommended by the Committee for Veterinary Medical Products (CVMP), a withdrawal time of 10 days was established for the safe use of the newly formulated colistin sulphate solution.

Key words: colistin, intramuscular administration, microbiological assay, residue depletion, swine, withdrawal time



“Full text available only in PDF format”




1. Bukhary Z, Mahmood W, Al-Khani A, Al-Abdely H M 2005 Treatment of nosocomial meningitis due to a multidrug resistant Acinetobacter baumannii with intraventricular colistin. Saudi Medical Journal 26: 656-658        [ Links ]

2. Chauvin C, Beloeil P A, Orand J P, Sanders P, Madec F 2002 A survey of group-level antibiotic prescriptions in pig production in France. Preventive Veterinary Medicine 109-120        [ Links ]

3. CVMP 1995 The European Agency for the Evaluation of Medicinal Products. Note for Guidance: Approach Towards Harmonization of Withdrawal Period EMEA/CVMP/036/95        [ Links ]

4. CVMP 2002 The European Agency for the Evaluation of Medicinal Products, Committee For Veterinary Medicinal Products, Colistin. Summary Report (2) EMEA/MRL/815/02-FINAL        [ Links ]

5. Decolin D, Leroy P, Nicolas A, Archimbault P 1997. Hyphenated liquid chromatographic method for the determination of colistin residues in bovine tissues. Journal of Chromatographic Science 35: 557-564        [ Links ]

6. Duenas D A I, Bratos Perez M A, Eiros Bouza J M, Almaraz Gomez A, Gutierrez-Rodriguez P, Miguel-Gomez M A, Orduna-Domingo A, Rodriguez-Torres A 2004. Susceptibility of the Acinetobacter calcoaceticus-A. baumannii complex to imipenem, meropenem, sulbactam and colistin. International Journal of Antimicrobial Agents 23: 487-493        [ Links ]

7. Fish D N, Piscitelli S C, Danziger L H 1995 Development of resistance during antimicrobial therapy: a review of antibiotic classes and patient characteristics in 173 studies. Pharmacotherapy 15: 279-291        [ Links ]

8. Govaerts C, Adams E, Van-Schepdael A, Hoogmartens J 200). Hyphenation of liquid chromatography to ion trap mass spectrometry to identify minor components in polypeptide antibiotics. Analytical and Bioanalytical Chemistry 377: 909-921        [ Links ]

9. Sato H, Ouchi M, Koumi J 1972 Distribution of colistin sulphate in the body. Distribution and metabolism of orally administered colistin sulphate in chickens and pigs. The Japanese Journal of Antibiotics 25: 239-245        [ Links ]

10. Kitagawa T, Ohtani W, Maeno Y, Fujiwara K, Kimura Y 1985 Sensitive enzyme immuno-assay of colistin and its application to detect residual colistin in rainbow trout tissue. Journal of Association of Official Analytical Chemists 68: 661-664        [ Links ]

11. Leroy P, Decolin D, Nicolas S, Archimbault P, Nicolas A 1989 Residue determination of 2 co-administered antibacterial agents -cephalexin and colistin - in calf tissues using high-performance liquid chromatography and microbiological methods. Journal of Pharmaceutic and Biomedical Analysis 7: 1837-1846        [ Links ]

12. Li J, Milne R W, Nation R L, Turnidge J D, Coulthard K, Johnson D W 2001 A simple method for the assay of colistin in human plasma, using pre-column derivatization with 9-fluorenylmethyl chloroformate in solid-phase extraction cartridges and reversed-phase high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications 761: 167-175        [ Links ]

13. Li J, Milne R W, Nation R L, Turnidge J D, Smeaton T C, Coulthard K 2004 Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate. Journal of Antimicrobial Chemotherapy 53: 837-840        [ Links ]

14. Li J, Nation R L, Milne R W, Turnidge J D, Coulthard K 2005 Evaluation of colistin as an agent against multi-resistant Gramnegative bacteria. International Journal of Antimicrobial Agents 25: 11-25        [ Links ]

15. Lin B, Zhang C, Xiao X 2005 Toxicity, bioavailability and pharmacokinetics of a newly formulated colistin sulphate solution. Journal of Veterinary Pharmacology and Therapeutics 28: 349-354        [ Links ]

16. Markou N, Apostolakos H, Koumoudious C, Athanasiou M, Koutsoukou A, Alamanos I, Gregorakos L 2003 Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients. Critical Care 7: R78-R83        [ Links ]

17. Orwa J A, Van Gerven A, Roets E 2000 Development and validation of a liquid chromatography method for analysis of colistin sulphate. Chromatographia 51: 433-436        [ Links ]

18. Orwa J A, Govaerts C, Busson R, Roets E, Van Schepdael A, Hoogmartens J 2001 Isolation and structural characterization of colistin components. Journal of Antibiotics 54: 595-599        [ Links ]

19. Senturk S 2005 Evaluation of the anti-endotoxic effects of polymyxin-E (colistin) in dogs with naturally occurred endotoxic shock. Journal of Veterinary Pharmacology and Therapeutics 28: 57-63        [ Links ]

20. USP 2005 Antibiotics-microbial assays. USP 29-NF24, p. 2513. Online at: (accessed May 2008).         [ Links ]

21. Westerman E M, Le Brun P P, Touw D J, Frijlink H W, Heijerman H G 2004. Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study. Journal of Cystic Fibrosis 3: 23-28        [ Links ]



Received: September 2008
Accepted: March 2009



*Author for correspondence. E-mail:

Creative Commons License All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License