Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of N-Acetylcysteine

  • Drug Disposition
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

N-Acetylcysteine is useful as a mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus. It is also used as an antidote to paracetamol (acetaminophen) poisoning and found to be effective for the prevention of car-diotoxicity by doxorubicin and hae norrhagic cystitis from oxazaphosphorines.

After an oral dose of N-acetylcysteine 200 to 400mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours. Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal. Information on absorption in the presence of food or other drugs is not available. The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours after the dose. Pharmacokinetic information is not available as to whether or not N-acetylcysteine crosses the blood-brain barrier or placenta, or into breast milk. Renal clearance has been reponed as 0.190 to 0.211 L/h/ke and approximately 70% of the total body clearance is nonrenal. Following oral administration, reduced /V-acetyl-cysteine has a terminal half-life of 6.25h. Little is known of the metabolism of this agent, although it is believed to be rapidly metabolised and incorporated on to proteins. The major excretory product is inorganic sulphate.

Frequently reported side effects are nausea, vomiting and diarrhoea. Biochemical and hae-matological adverse effects are observed but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, glutathione and anticancer agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anzai N, Kiura T, Chida S, Tanaka T, Takahashi H, et al. A sensitive fluorometric determination of N-acetylcysteine in biological fluids by HPLC. Journal of Pharmaceutical Sciences of Japan 101: 1002–1009, 1981

    CAS  Google Scholar 

  • Bowman G, Backer U, Larsson S, Melander B, Whalander L. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. European Journal of Respiratory Diseases 64: 405–415, 1983

    Google Scholar 

  • Bonanomi L, Gazzaniga A. Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. European Journal of Respiratory Diseases 61 (Suppl. 11): 45–51, 1980

    Google Scholar 

  • Borgstrom L, Kagedal B, Paulsen O. Pharmacokinetics of N-acetylcysteine in man. European Journal of Clinical Pharmacology 31: 217–222, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bronstein AC, Rumack BH. Acute acetaminophen overdose during pregnancy: review of fifty-five cases. Abstract. American Association of Poison Control Centers, October 7-12, 1984

  • Cotgreave IA, Eklund A, Larsson K, Moldeus P. No penetration of orally administered N-acetyltysteine into bronchoalveolar lavage fluid. European Journal of Respiratory Diseases 70: 73–77, 1987

    PubMed  CAS  Google Scholar 

  • Cotgreave IA, Moldeus P. Methodologies for the analysis of reduced and oxidized’ N-acetylcysteine in biological systems. Biopharmaceutical Drug Disposition 8: 365–375, 1987

    Article  CAS  Google Scholar 

  • DeCaro L, Ghizzi A, Costa R, Longo A, Ventresca GP, et al. Pharmacokinetics and bioavailability of oral acetylcysteine in healthy volunteers. Arzneimittel-Forschung 39: 382–386, 1989

    CAS  Google Scholar 

  • Drummer OH, Christophidis N, Horowitz JD, Louis WJ. Measurement of penicillamine and N-acetylcysteine in human blood by HPLC and electrochemical detection. Journal of Chromatography — Biomedical Applications 374: 251–257, 1986

    Article  PubMed  CAS  Google Scholar 

  • Frank H, Thiel D. Determination of N-acetylcysteine in biological fluids. Journal of Chromatography — Biomedical Applications 309: 261–267, 1984

    Article  PubMed  CAS  Google Scholar 

  • Hannestad U, Sorbo B. Determination of 3-mercaptolactate, mer-captoacetate and N-acetylcysteine in urine by gas chromatography. Clinica Chimica Acta 95: 189–200, 1979

    Article  CAS  Google Scholar 

  • Holdiness MR, Morgan LR, Gillen LE. HPLC determination of N-acetylcysteine in human serum following acetaminophen overdosage. Journal of Chromatography — Biomedical Applications 382: 99–106, 1986

    Article  PubMed  CAS  Google Scholar 

  • Johansson M, Westerlund D. Determination of N-acetylcysteine, intact and oxidized, in plasma by column liquid chromatography and post column derivatization. Journal of Chromatography 385: 343–356, 1987

    Article  PubMed  CAS  Google Scholar 

  • Kagedal B, Kallberg M, Martensson J. Determination of non-protein bound N-acetylcysteine in plasma by HPLC. Journal of Chromatography — Biomedical Applications 311: 170–175, 1984

    Article  PubMed  CAS  Google Scholar 

  • Klein-Schwartz W, Oderda GM. Adsorption of oral antidotes for acetaminophen poisoning (methionine and N-acetylcysteine) by activated charcoal. Clinical Toxicology 18: 283–290, 1981

    Article  PubMed  CAS  Google Scholar 

  • Kok WT, Halvax JJ, Frei RW. Comparison of electrochemical detection methods in liquid chromatography for determination of N-acetylcysteine in plasma. Journal of Chromatography 352: 27–33, 1986

    Article  PubMed  CAS  Google Scholar 

  • Lauterburg BH, Corcoran GB, Mitchell JR. N-acetylcysteine pro-teas against the hepatotoxicity of acetaminophen by reducing the reactive metabolites in rats in vivo. Gastroenterology 82: 1234, 1982

    Google Scholar 

  • Lewis PA, Woodward AJ, Maddock J. HPLC assay for N-acetylcysteine in plasma and urine. Journal of Pharmacuetical Sciences 73: 996–998, 1984

    Article  CAS  Google Scholar 

  • Lewis PA, Woodward AJ, Maddock J. Improved method for the determination of N-acetylcysteine in human plasma by HPLC. Journal of Chromatography 327: 261–267, 1985

    Article  PubMed  CAS  Google Scholar 

  • Maddock J. Biological properties of a cetylcysleine: assay development and pharmacokinetic studies. European Journal of Respiratory Diseases 61 (Suppl. Ill): 52–58, 1980

    Google Scholar 

  • Miller LF & Rumack BH. Clinical safety of high oral doses of acetylcysteine. Seminars in Oncology 10: 76–85, 1983

    PubMed  CAS  Google Scholar 

  • Moldeus P, Cotgreave IA, Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 50 (Suppl. 1): 31–42, 1986

    Article  PubMed  CAS  Google Scholar 

  • Morgan LR, Donley PJ, Harrison EF, Hunter HL. Protective effect of N-acetylcysteine on the urotoxicity produced by oxa-zaphosphosine without interference with anticancer activity. European Journal of Cancer and Clinical Oncology 18: 113–114, 1982

    Article  CAS  Google Scholar 

  • Morgan LR, Holdiness MR, Gillen LE. N-acetylcysteine: its bioavailability and interaction with ifosfamide metabolites. Seminars in Oncology 10: 56–61, 1983

    PubMed  CAS  Google Scholar 

  • Multicenter Study Group. Long term oral acetylcysteine in chronic bronchitis, a double blind controlled study. European Journal of Respiratory Diseases 61 (Suppl. Ill): 93–108, 1980

    Google Scholar 

  • Norpoth K. Studies on the metabolism of isophosphamide in man. Cancer Treatment Reports 60: 437–443, 1976

    PubMed  CAS  Google Scholar 

  • North DS, Peterson RG, Krenzelok EP. Effects of activated charcoal administration on acetylcysteine serum levels in humans. American Journal of Hospital Pharmacy 38: 1022–1024, 1981

    PubMed  CAS  Google Scholar 

  • Olsson B, Johansson M, Gabrielsson J, Holme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. European Journal of Clinical Pharmacology 34: 77–82, 1988

    Article  PubMed  CAS  Google Scholar 

  • Pirie NW, Hele TS. Studies in the sulphur metabolism of the dog. The preparation and metabolism of d-acetylcysteine. Biochemical Journal 27: 1716–1718, 1933

    PubMed  CAS  Google Scholar 

  • Prescott LF, Critchley JAJH. The treatment of acetaminophen poisoning. Annual Review of Pharmacology and Toxicology 23: 87–101, 1983

    Article  PubMed  CAS  Google Scholar 

  • Raggi MA, Cavrini V, DiPietra AM. Colorimetric determination of acetylcysteine, penicillamine, and mercaptopropionolgly-cine in pharmaceutical dosage forms. Journal of Pharmaceutical Sciences 71: 1384–1986, 1982

    Article  PubMed  CAS  Google Scholar 

  • Rodenstein D, DeCoster A, Gazzaniga A. Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders. Clinical Pharmacokinetics 3: 247–254, 1978

    Article  PubMed  CAS  Google Scholar 

  • Rodenstein D, DeCoster A, Gazzangia A. Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders. European Journal of Respiratory Diseases 61 (Suppl. Ill): 383–387, 1980

    Google Scholar 

  • Sheffner AL, Medler EM, Bailey KR, Gallo DG, Mueller A, et al. Metabolic studies wth acetylcysteine. Biochemical Pharmacology 15: 1523–1535, 1966

    Article  PubMed  CAS  Google Scholar 

  • Toyooka T, Imai K. HPLC and fluorometric detection of biologically important thiols, derivatized with ammonium 7-lluo-robenzo-2-oxa-1, 3-diazole-4-sulphonate. Journal of Chromatography 282: 495–500, 1983

    Article  CAS  Google Scholar 

  • Unverferth DV, Mehegan JP, Nelson RW, Scott CC, Leier CV, et al. The efficacy of N-acetylcysteine in preventing doxorubicin induced cardiomyopathy in dogs. Seminars in Oncology I ft 2-6, 1983a

  • Unverferth DV, Fertel RH, Balcerzak SP, Magorien RD, O’Dor-isio MS. N-acetylcysteine prevents the doxorubicin induced decrease of cyclic GMP. Seminars in Oncology 10: 49–52, 1983b

    PubMed  CAS  Google Scholar 

  • Ziment I. Acetylcysteine: a drug with an interesting past and a fascinating future. Respiration 50: 26–30, 1986

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lakeside Hospital, Metairie (New Orleans), Louisiana, USA

    Mack R. Holdiness

Authors
  1. Mack R. Holdiness
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holdiness, M.R. Clinical Pharmacokinetics of N-Acetylcysteine. Clin Pharmacokinet 20, 123–134 (1991). https://doi.org/10.2165/00003088-199120020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199120020-00004

Keywords

Search

Navigation