A comparative pharmacokinetic and tolerability analysis of the novel orotic acid salt form of tenofovir disoproxil and the fumaric acid salt form in healthy subjects

Figures & data

Figure 1 Mean serum tenofovir concentration–time profiles after a single oral administration of tenofovir disoproxil orotate (DA-2802 319 mg) or fumarate (TDF 300 mg) up to 72 hours post-dose (N=32) in linear scale. The inset shows the profile in semilog scale.

Figure 2 Individual serum tenofovir concentration–time profiles for (left) tenofovir disoproxil orotate (DA-2802 319 mg) and (right) fumarate (TDF 300 mg) up to 12 hours post-dosing after a single oral administration in linear scale (N=32).

Table 1 Pharmacokinetic parameters of tenofovir and statistical comparison between tenofovir disoproxil orotate (DA-2802 319 mg) and fumarate (TDF 300 mg) after a single oral administration

Parameters	Tenofovir disoproxil orotate (N=32)	Tenofovir disoproxil fumarate (N=32)	Geometric mean ratio (90% CI)a
Tmax (h)b	0.87 (0.50–2.00)	0.79 (0.50–2.00)	–
Cmax (ng/mL)c	264.53±96.10 (247.87)	284.19±73.99 (275.94)	0.898 (0.815–0.990)
AUC0–t (ng × h/mL)c	1,874.73±542.85 (1,793.10)	2,039.10±493.74 (1,982.67)	0.904 (0.836–0.978)
AUC0–inf (ng × h/mL)c	2,111.51±559.86 (2,035.30)	2,251.90±485.93 (2,203.27)	0.924 (0.863–0.989)
t1/2 (h)	20.45±4.56	19.56±3.47	–
CL/F (L/h)	165.71±66.42	139.18±28.91	–

Notes: Data expressed as arithmetic mean ± standard deviation, unless stated otherwise.

a Geometric mean ratio calculations of orotate to fumarate based on log-transformed data.

b Values expressed as median (minimum–maximum).

c Values expressed as arithmetic mean ± standard deviation (geometric mean). “–” indicates data not shown.

Abbreviations: AUC_0–t, area under the concentration-time curve to the last quantifiable concentration; AUC_0–inf, area under the serum concentration–time curve from time 0 to infinity; CI, confidence interval; C_max, maximum concentration; CL/F, apparent clearance; t_1/2, elimination half-life; T_max, time to reach C_max.

Figure 3 The tenofovir C_max (A) and AUC_0–t (B) after a single oral administration of tenofovir disoproxil orotate (DA-2802 319 mg) or fumarate (TDF 300 mg). Box plots show median values (solid horizontal lines across the boxes), 50th percentile values (solid horizontal box outline), 90th percentile values (whiskers), and individual values (closed circles).

Abbreviations: C_max, maximum concentration; AUC_0–t, area under the concentration-time curve to the last quantifiable concentration.

Figure S1 Spaghetti plots of individual (left) C_max and (right) AUC_0–t for comparison between tenofovir disoproxil orotate (DA-2802 319 mg) and fumarate (TDF 300 mg).

Abbreviations: C_max, maximum concentration; AUC_0–t, area under the concentration-time curve to the last quantifiable concentration.