The Suitability of Carbamazepine as a Single-Sample Probe of Human Mixed Function Oxidase Activity

Abstract

1. Carbamazepine concentrations measured in plasma and plasma ultrafiltrates by fluorescence polarization immunoassay (f.p.i.a.) from 0 to 48 h post-dose were used to calculate CL, V, clearance of plasma unbound drug (CL_unb), V_unb; mean(±SD) values for these were: 0.0171/kg/h (±0.004), 1.051/kg (±0.14), 0.0581/h/kg (±0.012), and 4.281/kg (±0.41), respectively.

2. A single-dose, single-sample procedure for estimating carbamazepine oral clearance was evaluated with a view to using carbamazepine as a probe in screening for host factor influences on human drug metabolism. Single sample estimates of carbamazepine clearance (CL) were closest to multiple sample values for carbamazepine clearance (CL) when blood samples were collected 48 h after carbamazepine ingestion. This was the case for plasma total carbamazepine and plasma unbound carbamazepine.

3. A value of 1.11/kg was used for V in calculating all single sample estimates of clearance (CL), and a value of 4.31/kg was used to calculate single sample estimates of clearance of plasma unbound drug (CL_unb). The mean prediction error (MPE) was negatively biased for CL and CL_unb values calculated from single carbamazepine concentrations in samples collected at 24, 36, and 48 h post-dose. MPE was less than 5% errant for CL and less than 1% errant for CL_unb when those parameters were calculated from 48 h concentrations of plasma total carbamazepine or plasma unbound carbamazepine, respectively. Root mean squared error (r.m.s.e.) was lost lowest when 48 h post-dose samples were used for single-sample clearance estimates.