Table 2.

Final population pharmacokinetic parameter estimates

Conjugated CPT				Free CPT
	Estimate (95% CI)	%RSE	Shr.		Estimate (95% CI)	%RSE	Shr.
Structural model
$V_1=V_{1,70kg}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^1$				$V_3=V_{3,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^1$
$V_{1,70\mathrm{kg}}(L)$	3.16 (2.91–3.40)	4%		$V_{3,70kg}(L)$	21.1 (12.9–30.5)	22%
$V_2=V_{2,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^1$				$V_4=V_{4,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^1$
$V_{2,70kg}(L)$	2.09 (1.89–2.32)	5%		$V_{4,70\mathrm{kg}}(L)$	19.4 (15.0-24.3)	13%
$Q_1=Q_{1,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^{0.75}$				$Q_3=Q_{3,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^{0.75}$
$Q_{1,70\mathrm{kg}}(L/h)$	0.0482 (0.0381–0.0617)	12%		$Q_{3,70\mathrm{kg}}(\mathrm{L}/\mathrm{h})$	25.6 (13.6–46.0)	33%
${\mathrm{CL}}_B={\mathrm{CL}}_{B,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^{0.75}$				${\mathrm{CL}}_3={\mathrm{CL}}_{3,70\mathrm{kg}}\times {\left(\frac{\mathrm{BW}}{70\mathrm{kg}}\right)}^{0.75}$
${\mathrm{CL}}_{B,70\mathrm{kg}}(L/h)$	0.0988 (0.0870–0.1129)	7%		${\mathrm{CL}}_{3,70\mathrm{kg}}(\mathrm{L}/\mathrm{h})$	0.874 (0.738–1.044)	9%
${\mathrm{CL}}_F(\mathrm{L}/\mathrm{h})$	5.71 (3.89–7.85)	18%
$t_{1/2}(\mathrm{h})$	0.307 (0.265–0.356)	8%
Random effects
${\mathrm{BSV}}_{V_1}(\mathrm{CV}\%)$	18.1 (12.3–24.7)	36%	6%	${\mathrm{BSV}}_{V_3}(\mathrm{CV}\%)$	79.8 (56.8–117)	42%	5%
${\mathrm{BSV}}_{V_1,{\mathrm{CL}}_B}(\mathrm{corr}.)$	0.918#			${\mathrm{BSV}}_{V_3,{\mathit{CL}}_3}(\mathrm{corr}.)$	0.884#
${\mathrm{BSV}}_{{\mathrm{CL}}_B}(\mathrm{CV}\%)$	33.5 (25.3–43.7)	29%	2%	${\mathrm{BSV}}_{{\mathit{CL}}_3}(\mathrm{CV}\%)$	42.2 (31.8–57.4)	33%	5%
${\mathrm{BSV}}_{{\mathrm{CL}}_F}(\mathrm{CV}\%)$	62.6 (44.2–86.4)	35%	5%
Residual error
${\mathrm{Bound}\mathrm{RE}}_{\mathrm{proportional}}(\%)$	12.3 (11.2–13.6)	10%	9%	${\mathrm{Free}\mathrm{RE}}_{\mathrm{proportional}}(\%)$	24.8 (22.3–28.1)	12%	10%
${\mathrm{Bound}\mathrm{RE}}_{\mathrm{additive}}(\mathrm{ng}/\mathrm{mL})$	5.07 (1.27–13.86)	64%	9%	${\mathrm{Free}\mathrm{RE}}_{\mathrm{additive}}(\mathrm{ng}/\mathrm{mL})$	0.396 (0.061–0.852)	53%	10%

95% CIs for parameter estimates were obtained via the 2.5 and 97.5% quantile estimates calculated during the SIR analysis

Conjugated CPT parameters: V₁ central volume of distribution, V₂ peripheral volume of distribution, Q₁ inter–compartmental clearance (V₁ − V₂), CL_B base conversion rate of conjugated CPT to free CPT (V₁ – V₃), CL_F time-dependent rate conversion of conjugated CPT to free CPT (V₁ – V₃), t_1/2 half-life of first-order decay scalar term governing CL_F-mediated CPT conversion

Free CPT parameters: V₃ central volume of distribution, V₄ peripheral volume of distribution, Q₃ inter-compartmental clearance (V₃ − V₄), CL₃ clearance of free CPT from V₃

Population estimates V_1,70 kg, V_2,70 kg, Q_1,70 kg, CL_B,70 kg, V_3,70 kg, V_4,70 kg, Q_3,70 kg, and CL_3,70 kg correspond to a 70 kg subject and are adjusted to individual values using the corresponding parameter formulas

CI confidence interval, %RSE percent relative standard error, Shr shrinkage, BW body weight, BSV between-subject variability, RE residual error, corr correlation coefficient

^#Correlation coefficient for specified covariance term is reported without 95% CI or %RSE