Pharmacokinetics of N-acetylcysteine after oral and intravenous administration to healthy cats

Jennifer L. Buur College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766.

Search for other papers by Jennifer L. Buur in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Pedro P. V. P. Diniz College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766.

Search for other papers by Pedro P. V. P. Diniz in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Kursten V. Roderick Angell Animal Medical Center, 350 S Huntington Ave, Boston, MA 02130.

Search for other papers by Kursten V. Roderick in
Current site
Google Scholar
PubMed
Close
 DVM
,
Butch KuKanich Department of Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

Search for other papers by Butch KuKanich in
Current site
Google Scholar
PubMed
Close
 DVM
, and
John H. Tegzes College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766.

Search for other papers by John H. Tegzes in
Current site
Google Scholar
PubMed
Close
 VMD

Abstract

Objective—To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration.

Animals—6 healthy cats.

Procedures—In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis.

Results—Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%.

Conclusions and Clinical Relevance—The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.

Abstract

Objective—To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration.

Animals—6 healthy cats.

Procedures—In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis.

Results—Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%.

Conclusions and Clinical Relevance—The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.

Contributor Notes

Supported in part by the Western University of Health Sciences Competitive Intramural Grant Program and the Morris Animal Foundation Veterinary Student Scholar Program.

Presented as a poster presentation at the Morris Animal Foundation–Small Companion Animal Symposium, Denver, June 2011.

The authors thank Drs. David Clark and Marc Togneri for technical assistance.

Address correspondence to Dr. Buur (jbuur@westernu.edu).
  • 1. Zafarullah M, Li WQ, Sylvester J, et al. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 2003; 60: 620.

  • 2. Holdiness MR. Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet 1991; 20: 123134.

  • 3. Villar D, Buck WB, Gonzalez JM. Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats. Vet Hum Toxicol 1998; 40: 156162.

    • Search Google Scholar
    • Export Citation
  • 4. Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev 1998; 3: 114127.

  • 5. Webster CR, Cooper J. Therapeutic use of cytoprotective agents in canine and feline hepatobiliary disease. Vet Clin North Am Small Anim Pract 2009; 39: 631652.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol (Phila) 2009; 47: 8188.

  • 7. Borgstrom L, Kagedal B, Paulsen O. Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 1986; 31: 217222.

  • 8. Shen F, Coulter CV, Isbister GK, et al. A dosing regimen for immediate N-acetylcysteine treatment for acute paracetamol overdose. Clin Toxicol (Phila) 2011; 49: 643647.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Kirschvink N, Fievez L, Bougnet V, et al. Effect of nutritional antioxidant supplementation on systemic and pulmonary antioxidant status, airway inflammation and lung function in heaves-affected horses. Equine Vet J 2002; 34: 705712.

    • Search Google Scholar
    • Export Citation
  • 10. Sanderson SL. Taurine and carnitine in canine cardiomyopathy. Vet Clin North Am Small Anim Pract 2006; 36: 13251343, viiviii.

  • 11. Lombardi R, Rodriguez G, Chen SN, et al. Resolution of established cardiac hypertrophy and fibrosis and prevention of systolic dysfunction in a transgenic rabbit model of human cardiomyopathy through thiol-sensitive mechanisms. Circulation 2009; 119: 13981407.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Marian AJ, Senthil V, Chen SN, et al. Antifibrotic effects of antioxidant N-acetylcysteine in a mouse model of human hypertrophic cardiomyopathy mutation. J Am Coll Cardiol 2006; 47: 827834.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement