TABLE 3.

Pharmacokinetic parameters derived from the plasma d₃- and d₆-α-T enrichment percentages following oral d₃- and IV d₆-α-T administration during 3 interventions¹

Parameter	DLM fat interventions	IV d6-α-T	Compared with 0% fat,2P value	Oral d3-α-T	Compared with 0% fat,3P value	Oral d3- compared with IV d6-α-T,4P value	Interaction,5P value
Elimination rate, Ke	40% fat	0.023 ± 0.002	0.3062	0.020 ± 0.002	0.7828	0.0601	0.5609
	0% fat	0.021 ± 0.002		0.020 ± 0.002		0.4862
	0% fat-fast	0.026 ± 0.002	0.0551	0.021 ± 0.002	0.7353	0.0336*
Half-life, h	40% fat	30.9 ± 2.2	0.2264	34.2 ± 2.7	0.6058	0.1564	0.2066
	0% fat	34.5 ± 2.2		36.2 ± 2.7		0.4862
	0% fat-fast	29.0 ± 2.6	0.0982	40.4 ± 3.3	0.3273	0.0336
%Max (enrichment)	40% fat	23.5% ± 1.1%	0.1816	14.7% ± 0.9%	0.0008*	<0.0001*	0.0166*
	0% fat	24.9% ± 1.1%		18.1% ± 0.9%		<0.0001*
	0% fat-fast	25.4% ± 1.3%	0.6238	15.5% ± 1.0%	0.0082*	0.0004*
Tmax,6 h	40% fat	7.8 ± 0.6	0.1057	12.9 ± 1.3	0.9809	0.0306*	0.0003*
	0% fat	6.5 ± 0.7		12.9 ± 1.3		0.0005*
	0% fat-fast	9.0 ± 0.8	0.0055*	20.0 ± 1.4	<0.0001*	<0.0001*
AUC0–72 h,7 % · h	40% fat	1101 ± 46	0.9274	657 ± 39	0.0037*	<0.0001*	0.1032
	0% fat	1105 ± 47		781 ± 39		0.0001*
	0% fat-fast	1121 ± 50	0.6622	693 ± 43	0.0323*	<0.0001*
Fractional absorption (0–72 h)8	40% fat			61% ± 3%	0.0120*
	0% fat			70% ± 3%
	0% fat-fast			62% ± 4%	0.0370*

¹Pharmacokinetic (PK) parameters (mean ± SEM) were calculated as described in Methods from data shown in Figure 4A, C from women in the following interventions: 40% fat, n = 10; 0% fat, n = 10; and 0% fat, fasting 12 h, n = 7. Statistical analyses of the PK parameters derived from either d₆-α-T or d₃-α-T enrichment percentages were performed as described for Table 2. *Statistically significant values. Cmax, maximum concentration; DLM, defined liquid meal; K_e, post-Cmax elimination rate; IV, intravenous; Tmax, time of Cmax. The statistical analysis was carried out to answer the questions in the footnotes shown below.

²What is the effect of the intervention on the IV d₆-α-T dose PK parameter?

³What is the effect of the intervention on the oral d₃-α-T dose PK parameter?

⁴Are there differences in the IV compared with oral α-T responses for each PK parameter?

⁵Did the response differ between the intervention and the route (IV d₆-α-T and oral d₃-α-T) for the PK parameter?

⁶Tmax is postnadir for the IV dose.

⁷AUC_0–72 is calculated from the plasma d₆-α-T and d₃-α-T enrichments from 0 to 72 h.

⁸From the dual-isotope method (% absorption = oral AUC_0–72/IV AUC_0–72 × 100).