| Pharmacokinetics/pharmacodynamics
There are few studies on the pharmacokinetics of acetylcysteine with terminal half-life values of between 2.7 and 5.7 hours reported in adults [18]. In infants, gestational age 24.9–31.0 weeks, 2–11 hours after birth, mean elimination half-life was 11 hours (range 7.8–15.2), plasma clearance 37 mL/kg/h (range 13–62) and volume of distribution 573 mL/kg (range 167–1010 mL/kg). A steady-state concentration of acetylcysteine was reached in 2–3 days during a constant infusion. [19] The oral systemic bioavailability of – varied between 6 and 10% in adult volunteers [20, 21], with first-pass metabolism in the liver limiting systemic concentrations [18].
In vitro experiments on constipated mice and human meconium compared perflubron, surfactant, Tween-80, Gastrografin, Golytely, DNase, acetylcysteine 4%, Viokase and sodium chloride 0.9% [22]. For relieving constipation in vivo, Gastrografin enema was most efficacious. All agents were equally benign to the intestinal mucosa. In vitro, only acetylcysteine 4% and perflubron were less effective at decreasing meconium viscosity than sodium chloride 0.9%, with acetylcysteine 4% producing a 69% decrease in viscosity on immediate inspection, but 99% by 6 hours.
In another study in 48 puppies aged from 3 days to 3 months, acetylcysteine solutions from 2–20% were compared to sodium chloride 0.9%. Extensive fluid shifts with hyperaemia and multiple haemorrhages of the bowel mucosa were found after exposure to acetylcysteine 20%, with degree of injury varying inversely with the age and size. The severity of the mucosal injury was less with lower concentrations and there were no adverse events reported with the 4% solution. [23]
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