The Pharmacokinetic Profile and Bioavailability of Enteral N-Acetylcysteine in Intensive Care Unit

Abstract

Background and Objectives: N-acetylcysteine (NAC) is a mucolytic agent used to prevent ventilator-associated pneumonia in intensive care units. This study aimed to evaluate the oral bioavailability of NAC in critically ill patients with pneumonia, isolated acute brain injury and abdominal sepsis. Materials and Methods: This quantitative and descriptive study compared NAC’s pharmacokinetics after intravenous and enteral administration. 600 mg of NAC was administered in both ways, and the blood levels for NAC were measured. Results: 18 patients with pneumonia, 19 patients with brain injury and 17 patients with abdominal sepsis were included in the population pharmacokinetic modelling. A three-compartmental model without lag-time provided the best fit to the data. Oral bioavailability was estimated as 11.6% (95% confidence interval 6.3–16.9%), similar to bioavailability in healthy volunteers and patients with chronic pulmonary diseases. Conclusions: The bioavailability of enteral NAC of ICU patients with different diseases is similar to the published data on healthy volunteers.

N-acetylcysteine (NAC) and Its Role in Clinical Practice Management of Cystic Fibrosis (CF): A Review

“…A recent study [23] assessed enteral bioavailability, confirming previous findings [14,15]. Another important aspect of intravenous administration of NAC concerns the side effects that can occur during infusion of the drug, such as bronchospasm, hypotension, flushing, urticaria, and angioedema, which could be more serious or even fatal after an overdose of NAC (i.e., >3 g/day).…”

Biallelic variants in the SLC13A1 sulfate transporter gene cause hyposulfatemia with a mild spondylo‐epi‐metaphyseal dysplasia

“… 9 , 38 Intravenous NAC administration in our patient restored plasma sulfate levels, demonstrating that NAC is indeed a source of free sulfate, including extracellular sulfate, and perhaps explaining its efficacy in preventing acetaminophen hepatotoxicity, an action currently attributed solely to the replenishment of anti‐oxidant glutathione. 36 Bearing in mind the low bioavailability of about 10% 39 in combination with the renal sulfate loss in the patient it remains to be demonstrated whether oral NAC treatment can restore sulfate levels as well.…”

N-Acetylcysteine Regenerates In Vivo Mercaptoalbumin

“…The concentration of NAC given at a dose of 600 mg by i.v. bolus is reported to be 36.1 mg/L (220 µmol/L) [ 36 ]; therefore, we can calculate that almost 3 moles of NAC are required to reduce 1 mole of cysteinylated albumin when given by i.v. bolus.…”

“…infusion, we then tested the efficacy of an equimolar dose of NAC given by oral administration. NAC has a limited bioavailability, which is reported to be almost 10% in both healthy and intensive care unit patients [ 36 , 37 ]. The plasma concentration of NAC after a bolus of 600 mg is 36.1 µg/mL [ 36 ], while after an oral dose of an equal amount, it reaches a Cmax of 2.5 µg/mL with a Tmax of 1–2 h [ 38 , 39 ].…”

“…NAC has a limited bioavailability, which is reported to be almost 10% in both healthy and intensive care unit patients [ 36 , 37 ]. The plasma concentration of NAC after a bolus of 600 mg is 36.1 µg/mL [ 36 ], while after an oral dose of an equal amount, it reaches a Cmax of 2.5 µg/mL with a Tmax of 1–2 h [ 38 , 39 ]. Based on the limited oral bioavailability of NAC, we expected to detect an effect of orally administered NAC much lower than that observed after the i.v.…”