TABLE 2.

AP and PP pharmacokinetic parameters (arithmetic mean ± S.D., n = 4) of DIG in M. nemestrina after intra-arterial (10 μg/kg) or oral (100 μg/kg) administration of the drug

Parameters	Unit	Intra-Arterial			Oral
		APa	PP	Geometric Mean Ratiob	AP	PP	Geometric Mean Ratio
C0/dose	ng/ml/μg	0.14 ± 0.12	0.12 ± 0.04	1.04 (0.65–1.46)	N.A.	N.A.	N.A.
Cmax/dose	pg/ml/μg	N.A.	N.A.	N.A.	4.20 ± 1.43	3.70 ± 1.63	1.07 (0.82–1.48)
Tmax	h	N.A.	N.A.	N.A.	1.75 ± 0.30	2.15 ± 2.59	0.89 (0.57–1.99)
AUC0-∞/dose	h*ng/ml/mg	0.14 ± 0.05	0.17 ± 0.04	0.91 (0.74–1.12)	0.14 ± 0.05	0.17 ± 0.04	1.09 (0.89–1.34)
CL	l/h	7.53 ± 2.47	6.02 ± 1.46	1.09 (0.89–1.34)	N.A.	N.A.	N.A.
CL	l/h/kg	0.93 ± 0.27	0.86 ± 0.21	1.03 (0.85–1.24)	N.A.	N.A.	N.A.
CL/F	l/h	N.A.	N.A.	N.A.	10.5 ± 4.89	9.29 ± 0.67	1.02 (0.84–1.33)
CL/F	l/h/kg	N.A.	N.A.	N.A.	1.28 ± 0.52	1.24 ± 0.08	0.99 (0.83–1.18)
Clrc	l/h	2.75 ± 0.95	2.61 ± 1.23	1.04 (0.82–1.32)	1.94 ± 1.32	2.25 ± 1.08	0.91 (0.64–1.70)
Clr	l/h/kg	0.35 ± 0.15	0.37 ± 0.17	0.98 (0.75–1.28)	0.23 ± 0.14	0.30 ± 0.16	0.88 (0.63–1.23)
fu	%	79.1 ± 6.48	77.7 ± 4.91	0.98 (0.92–1.06)	77.4 ± 4.64	73.4 ± 2.78	1.02 (0.99–1.05)
CLu	l/h	9.38 ± 2.42	7.76 ± 1.92	1.00 (0.36–2.84)	N.A.	N.A.	N.A.
CLu	l/h/kg	1.16 ± 0.27	1.11 ± 0.27	0.96 (0.82–1.14)	N.A.	N.A.	N.A.
CLu/F	l/h	N.A.	N.A.	N.A.	13.5 ± 6.28	12.3 ± 0.89	1.00 (0.82–1.34)
CLu/F	l/h/kg	N.A.	N.A.	N.A.	1.65 ± 0.67	1.69 ± 0.11	0.96 (0.81–1.15)
Clr unbound	l/h	3.50 ± 1.23	3.40 ± 1.70	1.09 (0.76–1.58)	2.50 ± 1.69	2.25 ± 1.08	0.89 (0.63–1.70)
Clr unbound	l/h/kg	0.45 ± 0.19	0.49 ± 0.23	1.05 (0.58–1.87)	0.32 ± 0.18	0.41 ± 0.20	0.85 (0.61–1.18)
Vss	l	171 ± 44.3	177 ± 48.8	0.99 (0.84–1.16)	N.A.	N.A.	N.A.
Vss	l/kg	21.6 ± 7.22	25.3 ± 6.36	0.93 (0.77–1.13)	N.A.	N.A.	N.A.
F	%	N.A.	N.A.	N.A.	67.9 ± 29.1	65.8 ± 19.9	1.00 (0.81–1.39)
t1/2	h	22.4 ± 8.19	25.8 ± 7.53	0.93 (0.73–1.19)	27.7 ± 5.27	32.5 ± 1.12	0.93 (0.84–1.17)
Urinary recoveryd	%	37.3 ± 13.6	34.8 ± 8.97	1.02 (0.81–1.28)	15.8 ± 13.2	20.9 ± 9.79	0.89 (0.67–1.54)

N.A., not applicable; f_u, percentage of unbound in plasma; CL_u, unbound plasma clearance; CL_u/F, unbound oral plasma clearance; F, bioavailability; t_1/2, terminal plasma half-life

^aIntra-arterial DIG PK study was performed in three instead of four pregnant macaques (n = 3)

^bGeometric mean ratio was presented as the ratio of AP/PP with 95% confidence interval in parentheses

^cCl_r, renal clearance was calculated as the ratio of the amount of DIG excreted in the urine in 72 h over AUC_{0–72 h}

^d72-h urinary recovery of the dose