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PubMed1996

Chromium(VI) Forms Thiolate Complexes with gamma-Glutamylcysteine, N-Acetylcysteine, Cysteine, and the Methyl Ester of N-Acetylcysteine.

Reaction of potassium dichromate with gamma-glutamylcysteine, N-acetylcysteine, and cysteine in aqueous solution resulted in the formation of 1:1 complexes of Cr(VI) with the cysteinyl thiolate ligand. The brownish red Cr(VI)-amino acid/peptide complexes exhibited differential stability in aqueous solutions at 4 degrees C and ionic strength = 1.5 M, decreasing in stability in the order: gamma-glutamylcysteine > N-acetylcysteine > cysteine. (1)H, (13)C, and (17)O NMR studies showed that the amino acids act as monodentate ligands and bind to Cr(VI) through the cysteinyl thiolate group, forming RS-Cr(VI)O(3)(-) complexes. No evidence was obtained for involvement of any other possible ligating groups, e.g., amine or carboxylate, of the amino acid/peptide in binding to Cr(VI). EPR studies showed that chromium(V) species at g = 1.973-4 were formed upon reaction of potassium dichromate with gamma-glutamylcysteine and N-acetylcysteine. Reaction of potassium dichromate or sodium dichromate with N-acetylcysteine and the methyl ester of N-acetylcysteine in N,N-dimethylformamide (DMF) also led to the formation of RS-Cr(VI)O(3)(-) complexes as determined by UV/vis, IR, and (1)H NMR spectroscopy. Thus, an early step in the reaction of Cr(VI) with cysteine and cysteine derviatives in aqueous and DMF solutions involves the formation of RS-CrO(3)(-) complexes. The Cr(VI)-thiolate complexes are more stable in DMF than in aqueous solution, and their stability towards reduction in aqueous solution follows the order cysteine < N-acetylcysteine < gamma-glutamylcysteine < glutathione.

Journal Article↗
PubMed1998

Analysis of cysteine and N-acetylcysteine in human plasma by high-performance liquid chromatography at the basal state and after oral administration of N-acetylcysteine.

A high-performance liquid chromatographic method for the determination of free reduced cysteine and N-acetylcysteine in human plasma at the basal state and after oral administration of N-acetylcysteine is described. The method is based on acid-catalysed conversion of plasma thiols to the corresponding S-nitroso derivatives by excess of nitrite and their subsequent cation-pairing RP-HPLC with detection at 333 nm. Recovery rates of cysteine and N-acetylcysteine added to human plasma were 94.6 and 99.6%, respectively. Inter- and intra-day precision were below 6%. In healthy humans (n = 5), free reduced cysteine was determined to be (mean+/-S.E.) 10.0+/-0.96 microM. No N-acetylcysteine was detected in plasma of these subjects above the limit of detection (e.g. 170 nM). The method was successfully applied to a pharmacokinetic study on orally administered N-acetylcysteine to healthy volunteers.

Acetylcysteine↗
PubMed1986

A procedure for the analysis of S-benzyl-N-acetylcysteine and S-(o-methylbenzyl)-N-acetylcysteine in human urine.

Analytical methods for mercapturic acids, the end-products of glutathione metabolism of the industrial solvents toluene and o-xylene (i.e., S-benzyl-N-acetylcysteine and S-(o-methylbenzyl)-N-acetylcysteine), added to human urine have been developed. The sensitivity is 2 ng/microliter (R.S.D. = +/- 13%) and 1 ng/microliter (R.S.D. = +/- 6.4%) urine for S-benzyl-N-acetylcysteine and S-(o-methylbenzyl-N-acetylcysteine, respectively, when using the h.p.l.c. method. The corresponding sensitivities for the g.l.c.-mass spectrometric method are 0.5 and 0.3 ng/microliter urine, respectively.

Acetylcysteine↗
PubMed1988

Human pharmacokinetics of erythromycin propionate-N-acetylcysteinate: comparative evaluation with erythromycin stearate and N-acetylcysteine.

The pharmacokinetic pattern of erythromycin propionate-N-acetylcysteinate (EPAC) (erythromycin stinoprate I.N.N.), a new derivative, was studied on 12 healthy volunteers after single and multiple oral treatments. Microbiological and/or HPLC analytical methods were used to titer either erythromycin as base, propionate and total or N-acetylcysteine (NAC). In the acute experiment, a comparative evaluation was performed with erythromycin stearate (ES) and with N-acetylcysteine, according to a randomized-multi-crossover design. EPAC showed a better bioavailability than ES with longer-lasting serum levels of active antibiotic. NAC concentrations in the serum after EPAC were practically identical to those found after an oral administration of NAC alone. The multiple treatment study, performed in the same 12 volunteers with only EPAC, indicated that the pharmacokinetic pattern is somewhat different from that observed after a single dose, since higher concentrations were present at the steady state conditions.

Acetylcysteine↗
PubMed1995

A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.

A newly synthesized mucolytic agent, N-acetylcysteine L-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), transepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and CI- content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF. Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in CI- content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions.

Acetylcysteine↗
PubMed2006

Acetylcysteine In Diabetes (AID): a randomized study of acetylcysteine for the prevention of contrast nephropathy in diabetics.

BACKGROUND: Patients with diabetes mellitus (DM) are at increased risk of contrast-associated nephropathy irrespective of their baseline creatinine (Cr). We tested the efficacy of N-acetylcysteine (NAC) relative to hydration in unselected patients (irrespective of baseline Cr) with DM. METHODS: We conducted a randomized open-label study comparing hydration alone (combined oral and rapid intravenous hydration, n = 69) to NAC plus hydration (similar hydration protocol plus NAC 600 mg BID x 4 doses, n = 68) in diabetic patients (mean age 65 +/- 10 years, 65% men) undergoing elective coronary angiography. The primary end point was the mean change in serum Cr measured up to 96 hours postangiography. RESULTS: Baseline Cr was 1.14 +/- 0.43 mg/dL (Cr > or = 1.3 mg/dL in 37 subjects). Baseline characteristics including blood urea nitrogen, Cr, and contrast volume were similar between the 2 groups. The mean Cr change in the NAC group was 0.14 +/- 0.47 versus 0.08 +/- 0.11 mg/dL in the hydration only group (P = NS). Contrast-associated nephropathy, defined as a > or = 0.5 mg/dL increase in Cr, was significantly more common in the NAC group, 9.2% versus 1.4%, P = .043. Similar results were found in the subgroup of participants with either an increased baseline serum Cr (> or = 1.3 mg/dL) or in those receiving high contrast volumes (> 100 mL). CONCLUSIONS: N-Acetylcysteine provides no benefit over an aggressive hydration protocol in patients with DM undergoing coronary angiography.

Acetylcysteine↗
PubMed2006

N-acetylcysteine and sodium bicarbonate versus N-acetylcysteine and standard hydration for the prevention of radiocontrast-induced nephropathy following coronary angiography.

BACKGROUND: Radiocontrast-induced nephropathy (RCIN) is thought to be caused by renal ischemia and direct toxic effects on renal tubular cells brought on by contrast media. The combination of N-acetylcysteine (NAC) and hydration fluids (NaCl 0.9% or 0.45%) has been shown to reduce these deleterious effects and is commonly given prior to coronary angiography. The use of bicarbonate as the hydration anion has been shown to confer additional RCIN protection compared with that of saline. However, limited data are available regarding whether sodium bicarbonate hydration, proven to be beneficial alone, can further improve outcomes when given with NAC. OBJECTIVE: To compare the incidence of RCIN in patients undergoing coronary angiography after pretreatment with NAC plus sodium bicarbonate hydration or NAC plus standard hydration (NaCl 0.9% or 0.45%). METHODS: A retrospective, single-center study evaluated 96 patients who underwent coronary angiography from January 2002 to December 2005. Data were collected through electronic chart reviews. RESULTS: Forty-seven patients received NAC and sodium bicarbonate for hydration and 49 received NAC and standard hydration. Baseline characteristics between the 2 groups were similar. All patients received at least one 600 mg oral dose of NAC before angiography was performed. RCIN was defined as impairment of renal function occurring within 72 hours of administering contrast media, indicated by an absolute increase in the serum creatinine level of 0.5 mg/dL or more. A total of 12.2% of the patients receiving NAC and standard hydration developed RCIN, versus 14.9% of the patients in the NAC and sodium bicarbonate group (p = 0.713). CONCLUSIONS: The addition of sodium bicarbonate to NAC does not appear to confer additional protection against the development of RCIN. Prospective, randomized, placebo-controlled trials are warranted to definitively determine how this combination compares with NAC and standard hydration in preventing RCIN.

Acetylcysteine↗
PubMed1983

Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo.

N-Acetylcysteine is the drug of choice for the treatment of an acetaminophen overdose. It is thought to provide cysteine for glutathione synthesis and possibly to form an adduct directly with the toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine. However, these hypothese have not been tested in vivo, and other mechanisms of action such as reduction of the quinoneimine might be responsible for the clinical efficacy of N-acetylcysteine. After the administration to rats of acetaminophen (1 g/kg) intraduodenally (i.d.) and of [(35)S]-N-acetylcysteine (1.2 g/kg i.d.), the specific activity of the N-acetylcysteine adduct of acetaminophen (mercapturic acid) isolated from urine and assayed by high pressure liquid chromatography averaged 76+/-6% of the specific activity of the glutathione-acetaminophen adduct excreted in bile, indicating that virtually all N-acetylcysteine-acetaminophen originated from the metabolism of the glutathione-acetaminophen adduct rather than from a direct reaction with the toxic metabolite. N-Acetylcysteine promptly reversed the acetaminophen-induced depletion of glutathione by increasing glutathione synthesis from 0.54 to 2.69 mumol/g per h. Exogenous N-acetylcysteine did not increase the formation of the N-acetylcysteine and glutathione adducts of acetaminophen in fed rats. However, when rats were fasted before the administration of acetaminophen, thereby increasing the stress on the glutathione pool, exogenous N-acetylcysteine significantly increased the formation of the acetaminophen-glutathione adduct from 57 to 105 nmol/min per 100 g. Although the excretion of acetaminophen sulfate increased from 85+/-15 to 211+/-17 mumol/100 g per 24 h after N-acetylcysteine, kinetic simulations showed that increased sulfation does not significantly decrease formation of the toxic metabolite. Reduction of the benzoquinoneimine by N-acetylcysteine should result in the formation of N-acetylcysteine disulfides and glutathione disulfide via thiol-disulfide exchange. Acetaminophen alone depleted intracellular glutathione, and led to a progressive decrease in the biliary excretion of glutathione and glutathione disulfide. N-Acetylcysteine alone did not affect the biliary excretion of glutathione disulfide. However, when administered after acetaminophen. N-acetylcysteine produced a marked increase in the biliary excretion of glutathione disulfide from 1.2+/-0.3 nmol/min per 100 g in control animals to 5.7+/-0.8 nmol/min per 100 g. Animals treated with acetaminophen and N-acetylcysteine excreted 2.7+/-0.8 nmol/min per 100 g of N-acetylcysteine disulfides (measured by high performance liquid chromatography) compared to 0.4+/-0.1 nmol/min per 100 g in rats treated with N-acetylcysteine alone. In conclusion, exogenous N-acetylcysteine does not form significant amounts of conjugate with the reactive metabolite of acetaminophen in the rat in vivo but increases glutathione synthesis, thus providing more substrate for the detoxification of the reactive metabolite in the early phase of an acetaminophen intoxication when the critical reaction with vital macromolecules occurs.

Acetaminophen↗
PubMed1994

Influence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study.

OBJECTIVES: Deactivation of endothelium-derived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow. We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger, N-acetylcysteine, would improve whole-body oxygen consumption (VO2), gastric intramucosal pH, and veno-arterial CO2 gradient (veno-arterial PCO2) during septic shock. DESIGN: Prospective, randomized, double-blind study conducted over 2 yrs. SETTING: Septic shock patients admitted to the intensive care unit. PATIENTS: Fifty-eight patients requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to septic shock, were included in this study. All patients were examined within 72 hrs after the onset of sepsis. They were optimally resuscitated by conventional means with volume and inotropic agents, and exhibited stable clinical conditions (hemodynamic values, body temperature, hemoglobin, FIO2). INTERVENTIONS: A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects randomly received either 150 mg/kg of intravenous N-acetylcysteine or placebo over a 15-min period, then a continuous infusion of 12.5 mg/hr of N-acetylcysteine or placebo over approximately 90 mins. MEASUREMENTS: Infusion measurements were begun 60 mins after the beginning of infusion and lasted approximately 30 mins. The infusion was then discontinued and 2 hrs later the final measurements were taken. MAIN RESULTS: Basic patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation [APACHE] II scores, Multiple Organ Failure scores) did not differ significantly, nor did pre- and 2-hr postinfusion measurements differ between any of the groups. Thirteen (45%) patients responded (i.e., showed an increase in VO2 > 10%, reaching a mean of 19%) to the N-acetylcysteine infusion. The N-acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-arterial PCO2, an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. The N-acetylcysteine nonresponders, as well as the patients in the placebo group, did not show any significant changes in any of these variables. The N-acetylcysteine responders had a higher survival rate (69%) than the non-responders (19%) and were studied earlier after onset of sepsis (37 hrs) than the nonresponders (61 hrs). The only significant difference between the entire N-acetylcysteine group (which included responders plus nonresponders) and the placebo group was an increased VO2 in the entire N-acetylcysteine group during infusion measurements. CONCLUSIONS: N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increase in VO2 and gastric intramucosal pH and a decrease in veno-arterial PCO2. The higher survival rate in the N-acetylcysteine responders and the fact that half of the patients receiving N-acetylcysteine did not respond, suggests that, in some patients, sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. If analyzed by intention to treat, the N-acetylcysteine did not produce effects that were significantly different from the placebo. Whether the N-acetylcysteine challenge was merely diagnostic or whether N-acetylcysteine can be effective in the treatment of sepsis deserves further investigation.

Acetylcysteine↗
PubMed1999

Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning?

BACKGROUND: The optimal route and duration of administration for N-acetyl-cysteine in the management of acetaminophen (paracetamol) poisoning are controversial. It has been stated on the basis of a selected post-hoc analysis that oral N-acetylcysteine is superior to intravenous N-acetylcysteine in presentations later than 15 hours. AIM OF STUDY: To investigate the efficacy of intravenous or oral N-acetylcysteine. PATIENTS AND METHODS: We analyzed a series of acetaminophen poisonings treated with a protocol including activated charcoal and intravenous N-acetylcysteine. The outcomes assessed included use of N-acetylcysteine, adverse effects of intravenous N-acetylcysteine, and the occurrence of hepatotoxicity (transaminase > 1000 U/L). We incorporated these results in a meta-analysis of previously reported series of acetaminophen poisonings to compare the outcomes from intravenous and oral N-acetylcysteine use. RESULTS: Of 981 patients admitted over 10 years, 4% (40) presented later than 24 hours and 10% (100) had concentrations of acetaminophen that indicated a probable or high risk of hepatotoxicity. The 30 patients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those who did not. No patients received a liver transplant but 2 patients died (one after referral to a transplant unit and one just before). Adverse reactions to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta-analysis, those with probable or high risk concentrations had similar outcomes with intravenous (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administration. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), late (10-24 hours: 30 and 26%), and overall (0-24 hours: 16 and 19%) were all similar. The proportion of patients classified as presenting later than 10 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%). CONCLUSIONS: The differences claimed between oral and intravenous N-acetylcysteine regimes are probably artifactual and relate to inappropriate subgroup analysis. A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most patients with acetaminophen poisoning.

Acetaminophen↗
PubMed2006

Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning.

PURPOSE: The efficacy, safety, and cost issues that should be considered when deciding on the appropriate route of acetylcysteine for the treatment of patients with acetaminophen poisoning are reviewed. SUMMARY: Oral and i.v. acetylcysteine appear to be equally effective when given within 8-10 hours of acetaminophen overdose. Anaphylactoid reactions to i.v. acetylcysteine have generally been reported in 3-6% of acetaminophen-poisoned patients. Dosing errors and hyponatremia have occurred in pediatric patients receiving i.v. acetylcysteine. Several investigators found an increased rate of anaphylactoid reactions in patients treated with i.v. acetylcysteine whose pretreatment serum acetaminophen levels were nontoxic. Compounding i.v. acetylcysteine from the oral preparation is less expensive than using premade i.v. solution. State pharmacy laws dictate whether extemporaneous compounding of acetylcysteine from the oral formulation is allowed. Oral acetylcysteine administration has resulted in minimal anaphylactoid reactions and is safer than i.v. acetylcysteine. Oral therapy should preferentially be considered in patients with asthma or atopic histories. The most important factors to consider when selecting the route of acetylcysteine administration include individual susceptibility, the severity of acetaminophen toxicity, and the time interval between acetaminophen ingestion and initiation of acetylcysteine therapy. CONCLUSION: Oral acetylcysteine administered within 8-10 hours of acetaminophen overdose prevents liver toxicity in the majority of patients who tolerate it and have no contraindications to therapy. I.V. acetylcysteine should be administered when patients are treated more than 10 hours postingestion of acetaminophen overdose or have underlying conditions preventing oral treatment. Anaphylactoid reactions are rare and occur more frequently in patients treated with the i.v. preparation.

Acetaminophen↗
PubMed1999

N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA.

Although N-acetylcysteine is an antioxidant which has been expected to be a cancer chemopreventive agent, its safety and risk assessment have not been evaluated. N-acetylcysteine increased the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, whereas the amount of 8-oxodG in HP100, which is a hydrogen peroxide (H(2)O(2))-resistant cell line derived from HL-60, was not increased. To clarify the mechanism of cellular DNA damage, we investigated DNA damage and its site specificity induced by N-acetylcysteine, using (32)P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. N-acetylcysteine induced extensive DNA damage in the presence of Cu(II). The DNA cleavage was enhanced by piperidine treatment, suggesting that N-acetylcysteine plus Cu(II) caused not only deoxyribose phosphate backbone breakage but also base modification. N-acetylcysteine plus Cu(II) frequently modified thymine and guanine residues. Bathocuproine, a specific Cu(I) chelator, and catalase inhibited the DNA damage, indicating the participation of Cu(I) and H(2)O(2) in the DNA damage. Typical hydroxyl radical scavengers did not inhibit N-acetylcysteine plus Cu(II)-induced DNA damage, whereas methional completely inhibited it. These results suggest that reactive species derived from the reaction of H(2)O(2) with Cu(I) participates in N-acetylcysteine plus Cu(II)-induced DNA damage. The content of 8-oxodG in calf thymus DNA was increased by N-acetylcysteine in the presence of Cu(II). The present study has demonstrated that N-acetylcysteine could induce metal-dependent H(2)O(2) generation and, subsequently, damage to cellular and isolated DNA. Therefore, it is reasonable to consider that N-acetylcysteine may have the dual function of carcinogenic and anti-carcinogenic potentials. This work requires further studies on safety and risk assessment of N-acetylcysteine.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1991

Use of N-acetylcysteine in clinical toxicology.

The major use of N-acetylcysteine in clinical toxicology is in the treatment of acetaminophen (paracetamol) overdosage. The hepatorenal toxicity of acetaminophen is mediated by a reactive metabolite normally detoxified by reduced glutathione. If glutathione is depleted, covalent binding to macromolecules and/or oxidation of thiol enzymes can lead to cell death. Oral or intravenous N-acetylcysteine or oral D,L-methionine mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides; L-methionine also forms cysteine, thus giving rise to glutathione and other products. Oral therapy with N-acetylcysteine or methionine for acetaminophen poisoning is contraindicated in the presence of coma or vomiting, or if activated charcoal has been given by mouth. Nausea, vomiting, and diarrhea may also occur as a result of oral N-acetylcysteine administration. Anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into N-acetylcysteine infusion (20 hours intravenous regimen) in up to 10% of patients. Following accidental intravenous overdosage, the adverse reactions of N-acetylcysteine are similar but more severe; fatalities have occurred. A reduction in the loading dose of N-acetylcysteine may reduce the risk of adverse reactions while maintaining efficacy. Administration of N-acetylcysteine for a longer period might provide enhanced protection for patients in whom acetaminophen absorption or elimination is delayed. N-acetylcysteine may also have a role in the treatment of toxicity from carbon tetrachloride, chloroform, 1,2-dichloropropane, and other compounds. The possible use of N-acetylcysteine and other agents in the prevention of the neuropsychiatric sequelae of acute carbon monoxide poisoning is an important area for future research.

Acetaminophen↗
PubMed2005

A clinical and pharmacoeconomic justification for intravenous acetylcysteine: a US perspective.

Paracetamol (acetaminophen) poisoning remains the most common exposure reported to US poison information centres and the leading cause of poisoning-related fatalities, despite the availability of an effective antidote, acetylcysteine. Oral acetylcysteine solution has been approved for the management of acetaminophen poisoning in the US for four decades. Until the recent approval of intravenous acetylcysteine in the US, it was necessary to compound the oral solution for intravenous administration. The effectiveness and tolerability of oral and intravenous acetylcysteine for the prevention of hepatotoxicity induced by paracetamol poisoning are well established in the literature. Intravenous acetylcysteine may be preferred over oral administration based on improved tolerability, ease of administration and the shortened course of therapy (20 hours intravenous vs 72 hours oral). The two intravenous acetylcysteine regimens documented in the literature, 48 hours and 20 hours, have similar efficacy when started within 8-10 hours of ingestion. Although there are no legal concerns with continuing the routine compounding of the oral solution to an intravenous product, new standards for pharmacy compounding of sterile preparations set forth by the US Pharmacopoeia highlight that the risk of compounding products for intravenous use must be assessed carefully. Changing the route of administration of a sterile oral solution to an intravenous preparation, when a commercial sterile and pyrogen-free product is available, may not be advisable. The best cost-containment strategies must be used for introduction of the more costly sterile, pyrogen-free intravenous acetylcysteine formulation by hospitals and healthcare systems. The intravenous acetylcysteine product is more cost effective when given for 20 hours than other treatment protocols based on the costs of acetylcysteine and hospitalisation. If used per protocol, the 20-hour intravenous acetylcysteine regimen may decrease hospital length of stay, thereby, offsetting the increased drug cost. Data conflict on the efficacy and administration of intravenous acetylcysteine for off-label uses, such as radiographic contrast media-induced nephropathy prevention and reperfusion in orthotopic liver transplantation. The costs for the intravenous formulation for these indications is significantly higher than use of the oral formulation for oral administration in radiographic contrast media-induced nephropathy prevention and compounded for intravenous use in orthotopic liver transplantation. The oral solution should be retained by healthcare systems for oral and inhalation applications, such as respiratory conditions, oral administration for radiographic contrast media nephropathy prevention, or the use of the 72-hour oral protocol to treat paracetamol poisoning, when the intravenous preparation cannot be used.

Acetaminophen↗
PubMed1999

Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants.

BACKGROUND: Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants. The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates. This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group. METHODS: N-acetylcysteine was infused intravenously in ten patients (gestational age 24.9-31.0 weeks, weight 500-1384 g) for 24 h (3.4-4.6 mg/kg/h), starting 2.0-11.2 h from birth (study I) and in six patients (gestational age 25.9-29.7 weeks, weight 520-1335 g) for 6 days (0.3-1.3 mg/kg/h), starting at the age of 24 h (study II). Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed samples taken during (study I and II) and after (study I) the N-acetylcysteine infusion. RESULTS: In study I, the mean elimination half-life of N-acetylcysteine was 11 h (range 7.8-15.2 h). The mean plasma clearance of N-acetylcysteine was 37 ml/kg/h (range 13-62 ml/kg/h) and the mean volume of distribution was 573 ml/kg (range 167-1010 ml/kg). The plasma clearance and volume of distribution correlated with weight (r = 0.81, P < 0.01, and r = 0.78, P < 0.01, respectively) and with gestational age (r = 0.71, P < 0.05, and r = 0.64, P < 0.05, respectively). In study II, the steady-state concentration of N-acetylcysteine was reached in 2-3 days in five of six patients during a constant infusion. CONCLUSIONS: The pharmacokinetics of N-acetylcysteine in pre-term infants depend markedly on weight and gestational age. The elimination of N-acetylcysteine is much slower in pre-term new-borns than in adults.

Acetylcysteine↗