Effect of N-acetylcysteine on serum creatinine level

Hassane Izzedine1, Valérie Guerin2, Vincent Launay-Vacher1, Maguy Bernard2 and Gilbert Deray1

1 Department of Nephrology 2 Department of Biochemistry, Pitié-Salpêtrière Hospital, Paris, France

Sir,

When co-administration of a drug to another that is known to be nephrotoxic leads to a milder elevation of serum creatinine than that drug alone, it is necessary to verify that no analytical interaction occurs in the determination of serum creatinine [1]. N-acetylcysteine (NAC) was reported to improve renal function in patients with hepatorenal syndrome [2]. Recently, Tepel et al. [3] demonstrated that administration of NAC reduced contrast media nephrotoxicity. This demonstration was based on a milder elevation of serum creatinine following administration of contrast medium when associated with NAC. In the present study, to exclude a potential analytical interaction, NAC (final concentration 2.5 mmol/l, which is equivalent to 408 mg/l with a NAC molecular weight of 163.2) was added in vitro to plasma samples of patients, and serum creatinine was measured. There was no difference in serum creatinine concentration with or without NAC. After oral administration of a 400 mg NAC dose, maximum plasma NAC concentration has been reported to be 310 mg/l [4]. Assuming that its pharmacokinetics are linear for oral doses of 400–600 mg, NAC Cmax in Tepel's study would be expected to be around 465 mg/l, higher than the concentration tested for potential interaction. Therefore, we supplemented a pool of plasma samples (n=15) with NAC (Sigma, France). Dilutions of NAC were performed with NaCl 0.15 M to obtain final concentrations ranging from 0 to 600 mg/l, respecting a NAC/plasma ratio of 1/9 (vol./vol.). Serum creatinine was determined in duplicate using modified Jaffe method with kinetic measurement and dichromatic detection on a CX7 analyser (Beckman-Coulter, France). Values of creatinine levels have been plotted against NAC concentration in samples as shown in Figure 1Go. There was no analytical interference with creatinine determination for NAC concentrations ranging from 102 to 600 mg/l, corresponding to the potential range of in vivo plasma levels after a 600 mg oral administration every 12 h. However, at very high NAC concentration (>=50 g/l), we observed a 50% decrease in creatinine levels owing to analytical interaction. We thus confirm that the effect of NAC on contrast media nephrotoxicity, which was observed by Tepel et al., was not related to an analytical interaction between creatinine and NAC.



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Fig. 1. Plasma creatinine levels versus different plasma N-acetylcysteine concentrations.

 

References

  1. LeBel M, Paone RP, Lewis GP. Lack of interference of five new beta-lactam antibiotics with serum creatinine determination. Drug Intell Clin Pharm1983; 17: 908–910[ISI][Medline]
  2. Holt S, Goodier D, Marley R et al. Improvement in renal function in hepatorenal syndrome with N-acetylcysteine. Lancet1999; 353: 294–295[ISI][Medline]
  3. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med2000; 343: 180–184[Abstract/Free Full Text]
  4. Maddock J. Biological properties of acetylcysteine: assay development and pharmacokinetics studies. Eur J Resp Diseases1980; 61 [Suppl 111]: 52–58




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