Table 2.

Pharmacokinetic parameters measured over 72 hours (i.e., up to 24 hours after the last dose of administered disulfiram) in a model simulataneously including all metabolites.

	DSF (Disulfiram) RSE (%)a	M1 (DDTC) RSE (%)a	M2 (DDTC-Me) RSE (%)a	M3 (DETC-MeSO) RSE (%)a	M4 (Carbamathione) RSE (%)a
Final PK model parameters
CL/F (L/hr)b	−	−	0.580 (5.5)	0.595 (6.3)	−
CLintrinsic (L/hr)b	0.531 (7.7)	0.388 (6.7)	−	−	0.291 (4.1)
V (L)c	1.29 (9.1)	0.0906 (16.6)	0.00404 (8.0)	0.0647 (15.6)	0.581 (10.3)
Km (ng/mL)d	217 (9.3)	480 (6.2)	−	−	543 (4.3)
Ka (hr−1)e	0.0752 (4.3)	−	−	−	−
Qf	−	−	0.0776 (14.0)	−	−
Vperiph (L)g	−	−	28.9 (17.3)	−	−
Additive RE (ng/mL)	35.4 (7.1)	41.8 (12.4)	−	15.2 (5.3)	82.5 (8.5)
Proportional RE (%)	31.5 (9.7)	49.5 (5.0)	20.3 (10.1)	40.8 (7.1)	23.3 (19.6)
BV (%) in CL/F	36 (14)	−	−	−	−

Abbreviations: DSF = parent drug, disulfiram; M1 = metabolite 1; M2 = metabolite 2; M3 = metabolite 3; M4 = metabolite 4; DSF = disulfiram; DDTC = N,N-diethyldithiocarbamate; DDTC = diethyldithiocarbamate-methyl ester; DDTC-MeSO = S-methyl-N,N-diethylthiolcarbamate sulfoxide; PK = pharmacokinetic; CL = clearance; F = bioavailability; V = volume; RSE = residual standard error; BV = between-subject variability.

^aObtained by nonparametric bootstrap with 30 samples.

^bOral clearance: $\text{linear elimination}=\left(\frac{CL}{F}\right)$; $\text{non-linear elimination}=\left(\frac{V_{max}}{C+K_m}\times C\right)$ where V_max = CL_intrinsic ×K_m, C = concentration of analyte, K_m = is the Michaelis-Menten constant as defined below.

^cVolume of distribution.

^dMichaelis–Menten constant (concentration of drug at which elimination is half maximal).

^eAbsorption constant.

^fFlow from central compartment to periphery.

^gCalculated peripheral volume.