TABLE 1.

PK parameters of afabicin desphosphono in plasma and bone tissues and fluid after the third oral dose of afabicin in patients undergoing hip replacement surgery^d

Parameter	Value(s) for:
	Plasma (n = 14)	Sparse sampling (from n = 2–4 at each time of resection)
		Plasma	Cortical bone	Cancellous bone	Bone marrow	Soft tissue	Synovial fluid
AUCτ (ng·h/ml for fluids or ng·h/g for tissues)	20,400 (30.6)	20,100	4,240	8,040	7,060	6,790	12,300
C12 (ng/ml for fluids or ng/mg for tissues)	1,120 (43.4)	1,500	373	648	640	526	1,210
Cmax (ng/ml for fluids or ng/mg for tissues)	2,360 (28.0)	2,150	441	841	695	759	1,280
Ctrougha (ng/ml for fluids or ng/mg for tissues)	1,200 (36.7)	—	—	—	—	—	—
t1/2b (h)	11.8 (70.1)	—	—	—	—	—	—
tmax (median [range]) (h)	2 (0.5–2)	6	6	6	6	6	6
Penetration ratio
AUC for tissue/AUC for plasma	—	1	0.21	0.40	0.35	0.34	0.61
Cmax for tissue/Cmax for plasma	—	1	0.21	0.39	0.32	0.35	0.60
AUC for free tissue/AUC for free plasmac	—	1	—	—	—	—	2.88

^aC_trough was not obtained for bone resection-associated sparse sampling, as surgery occurred after the 3rd afabicin dose.

^bt_1/2 was not calculated for data obtained from sparse samples, as an elimination phase could not be characterized from the mean profile.

^cThe free fraction of afabicin desphosphono was 2% in plasma and 9.4% in synovial fluid.

^dAfabicin was administered at 240 mg q12h. Results are geometric means (geometric CV [in percent]) unless otherwise indicated. AUC_τ, area under the curve at steady state; C₁₂, concentration 12 h after the last dose; C_max, maximum observed plasma concentration; C_trough, measured concentration at the end of the dosing interval at steady state, just prior to the last dose; t_1/2, terminal elimination half-life; t_max, time of maximum observed plasma concentration; n, number of observations; —, no reportable data.