Pharmacokinetics/Pharmacodynamics study of Fixtral SB as compared to supra bioavailable itraconazole and conventional itraconazole

Table 1 Summary of pharmacokinetic variables determining bioequivalence for itraconazole – Test vs reference product (R2)

Variable	Geometric mean		T/R2 ratio (%), 90%CI	Outcome of BE result
	Test (T)	Reference (R2)
AUC0-t (ng × h/mL)	2533.47	2794.45	0.9066 (83.31% - 98.65%)	Bioequivalent
AUC0-inf (ng × h/mL)	2856.78	3212.68	0.8892 (81.57%– 96.92%)	Bioequivalent
Cmax (ng/mL)	117.4	118.82	0.988 (88.57%-110.22%)	Bioequivalent

T: Test; R2: Reference; BE: Bioequivalence; CI: Confidence interval; AUC_0-t: Area under the concentration-time curve over the dosing interval; AUC_0-inf: Area under the curve; C_max: Maximum concentration; T_max: Time to peak drug concentration.

Table 2 Mean pharmacokinetic parameters for test and reference product (R1 and R2) for itraconazole

Variable	mean ± SD
	Test (T)	Reference (R1)	Reference (R2)
Cmax (ng/mL)	132.12 (65.31)	308.57 (173.63)	136.90 (67.91)
AUC0-t	2738.083 (1164.121)	4953.205 (2472.121)	3065.766 (1295.989)
AUC0-inf	3109.578 (1342.394)	5744.760 (2917.508)	3614.170 (1850.356)
Tmax	11.45(6.05)	6.00 (1.49)	10.85 (6.33)
Kel	0.022 (0.007)	0.021 (0.007)	0.023 (0.008)
t1/2	34.89 (13.18)	37.83 (14.95)	35.16 (20.14)
Residual area	11.92 (7.41)	12.86 (7.86)	12.22 (9.10)

SD: Standard deviation; AUC_0-t: Area under the concentration-time curve over the dosing interval; AUC_0-inf: Area under the curve; C_max: maximum concentration; T_max: Time to peak drug concentration.

Table 3 Mean pharmacokinetic parameters for test and reference product (R1 and R2) for hydroxyitraconazole

Variable	mean ± SD
	Test	Reference (R1)	Reference (R2)
Cmax (ng/mL)	181.35 (58.30)	310.20 (11.63)	197.12 (56.84)
Tmax	12	8	12
Kel	0.050 (0.015)	0.043 (0.014)	0.050 (0.019)
t1/2	15.20 (4.92)	18.14 (7.10)	16.01 (6.55)
Residual area	2.72 (3.12)	4.31 (5.03)	3.37 (3.88)

SD: Standard deviation; T_max: Time to peak drug concentration; C_max: maximum concentration.