Table 2.
NAC PK parameters.
| Study | Dose | Form | Mean t½ (h) | Mean CL (or CL/F) (L/h/kg) |
Mean V (or V/F) L/kg |
Model/Notes |
|---|---|---|---|---|---|---|
| Börgstrom et al., 1986 [31] 10 adult HV |
600 mg IV 600 mg oral | Non- protein-bound NAC | 2.27 (IV) (elimination) | 0.211 | 0.33 | Bioavailability 6–10% |
| Olsson et al., 1988 [32] 6 HV |
200mg IV 400 mg oral |
Total NAC | 5.58 (IV) (terminal) | 0.19 | 0.47 | Total NAC concentrations declined in a triphasic manner. Bioavailability 9.1%. From one hour onward, covalent protein binding of NAC increased, reaching maximum 50% at 4 h, and decreased to 20% at 12 h post-dose |
| Prescott et al., 1989 [33] 17 patients of acetaminophen overdose |
150 mg/kg IV over 15 min followed by 50 mg/kg IV in 4 h, and 100 mg/kg over 16 h | Total NAC | 5.7 (±2.9) (terminal) |
0.19 | 0.54 | |
| Ahola et al., 1999 [34] 10 preterm infants |
4.2 mg/kg/h for 24 h (continuous IV infusion) | Total NAC | 11 (elimination) |
0.037 | 0.57 | |
| Weist et al., 2014 [35] 11 pregnant women 5 preterm infants 6 near-term infants |
100 mg/kg IV q4h 12.5 mg/kg q12h 25 mg/kg q12h |
Total NAC | 1.2 7.5 5.1 |
0.26 0.045 0.07 |
0.41 0.47 0.34 |
|
| Coles et al., 2017 [36] 4 patients with PD 3 HV |
Steady-state PK following 3000 mg oral NAC | Total NAC | 4.6 5.9 |
66.6 L/h | 269 L | NCA used for t½. Pop PK model first-order absorption, 1-compartment, proportional error model (estimated PD, HV together) |
| Papi et al., 2021 [37] 15 HV Chinese 15 HV Caucasian |
Oral effervescent tablet, NAC 600 mg first as a single dose and, following a 48 h wash-out period, twice daily for 3 days. | Total NAC | 15.4 ± 3.5 18.7 ± 7.2 |
1250.0 ± 474.9 1400.8 ± 508.5 |
56.9 ± 16.2 56.0 ± 20.1 |
Estimated Chinese and Caucasian separately. Accumulation ratio Chinese 1.5 ± 0.4 and Caucasian 1.4 ± 0.2. V, CL, t½ estimated after single dose, expressed as mean ± SD |
| Greene et al., 2016 [38] 29 HV effervescent NAC. 30 HV NAC solution 11g NAC oral dose in both periods |
A single-dose, randomized-sequence, 2-period crossover design with a 7-day washout period | Total NAC | 18.1 ± 3.96 17.5 ± 2.98 |
65.1 ± 22.8 59.3 ± 16.3 |
1720 ± 731 1510 ± 503 |
NCA µg/mL Cmax (oral solution, effervescent tablet, resp.) 28.4, 26.5 µg/mL, resp. Estimates of V/F are in L (not normalized to weight). Relative F = 94 ± 18.5 effervescent/solution ratio of AUCinf values × 100. |
| Liu et al., 2010 [39] 24 HV Chinese adults 3 × 200 mg test effervescent NAC. 600 mg effervescent oral NAC (reference: Fumicil®) |
A single-dose, randomized-sequence, 2-period crossover design with a 7-day washout period | Total NAC | 6.07 ± 2.41 5.62 ± 2.60 |
-- -- |
-- -- |
NCA |
Abbreviations: HV, healthy volunteers; PD, Parkinson’s disease; IV, intravenous; Pop PK, population pharmacokinetics; NCA, non-compartmental analysis; AUC, area under the curve; SD, standard deviation.