Table 2.

Univariate and multivariate analyses of factors affecting raltegravir pharmacokinetic parameters at standard and reduced doses

Parameter and variablea	Univariate analysis		Multivariate analysis
	Coefficient (95% CI)	P value	Coefficient (95% CI)	P value
AUC0-24
Dose of 400 mg QD (vs 400 mg BID)	0.64 (0.50–0.80)	<0.001	0.63 (0.50–0.80)	<0.001
Dose of 800 mg QD (vs 400 mg BID)	1.15 (0.92–1.44)	0.22	1.15 (0.92–1.45)	0.23
Atazanavir comedication	2.13 (1.15–3.96)	0.02	2.16 (1.18–3.25)	0.01
Darunavir comedication	0.67 (0.45–1.01)	0.054
Half-life
Dose of 400 mg QD (vs 400 mg BID)	1.79 (1.42–2.25)	<0.001	1.80 (1.42–2.29)	<0.001
Dose of 800 mg QD (vs 400 mg BID)	2.21 (1.77–2.76)	<0.001	2.20 (1.75–2.77)	<0.001
Tenofovir comedication	1.36 (0.99–1.86)	0.055	1.35 (1.03–1.77)	0.03
Darunavir comedication	1.34 (0.97–1.84)	0.076	1.34 (1.02–1.76)	0.04
Clearance
Dose of 400 mg QD (vs 400 mg BID)	0.78 (0.62–0.99)	0.04	0.79 (0.62–1.00)	0.05
Dose of 800 mg QD (vs 400 mg BID)	0.87 (0.69–1.09)	0.22	0.87 (0.69–1.09)	0.23
Atazanavir comedication	0.46 (0.25–0.84)	0.01	0.46 (0.25–0.85)	0.01
Darunavir comedication	1.53 (1.04–2.26)	0.03
Cmax
Dose of 400 mg QD (vs 400 mg BID)	1.28 (0.86–1.91)	0.22
Dose of 800 mg QD (vs 400 mg BID)	2.27 (1.54–3.33)	<0.001
Ctrough
Dose of 400 mg QD (vs 400 mg BID)	0.20 (0.13–0.31)	<0.001
Dose of 800 mg QD (vs 400 mg BID)	0.38 (0.25–0.59)	<0.001

^aAUC comparisons between twice-daily (BID) and once-daily (QD) dosing were made by first converting the AUC_0-12 to the AUC_0-24. The C_trough for BID dosing is C₁₂, and that for QD dosing is C₂₄. Only covariates significant in univariate analysis and doses are presented.