Table 4. Summary of pharmacokinetic parameter data.

	10 mg solution (n=5)	20 mg solution (n=3)	40 mg solution (n=6)	40 mg tablet (n=7)	60 mg tablet (n=7)	90 mg tablet (n=11)	120 mg tablet (n=10)
Following single dose
Cmax (ng ml−1)
Gmean (range)	16.8 (13.5–25.0)	27.0 (16.2–72.5)	70.9 (37.4–102)	72.3 (25.5–148)	57.1 (18.3–341)	70.1 (16.9–322)	177 (22.0–538)
% CV	29.3	91.9	34.3	48.3	121.0	94.2	68.5
AUC (ng h ml−1)
Gmean (range)	24.5 (16.5–35.5)	43.7 (22.7–79.3)	101 (63.8–212)	127 (40.4–240)	136 (31.8–429)	134 (27.5–460)	294 (122–530)
% CV	33.2	57.5	49.1	48.5	75.0	76.0	47.0
AUC0–12 (ng h ml−1)
Gmean (range)	24.1 (16.2–35.4)	43.3 (22.6–78.6)	99.4 (63.5–208)	124 (40.3–230)	131 (31.3–419)	130 (27.4–427)	280 (104–525)
%CV	33.2	57.4	48.7	46.8	76.0	75.0	47.0
CL/F (l h−1)
Amean (range)	426 (282–608)	522 (252–882)	424 (189–627)	382 (167–989)	604 (140–1890)	946 (196–3280)	473 (227–984)
S.d.	139	325	152	291	591	895	283
Vss/F (l)
Amean (range)	884 (547–1200)	1049 (460–1500)	840 (434–1260)	762 (406–1880)	1767 (320–4320)	2454 (582–6570)	1372 (376–5070)
S.d.	281	533	329	506	1406	2103	1378
t1/2 (h)
Amean (range)	2.43 (1.73–3.31)	1.86 (1.25–2.18)	2.65 (1.75–4.32)	2.28 (1.53–4.04)	2.37 (1.41–2.89)	2.36 (1.35–5.37)	3.14 (1.82–7.73)
S.d.	0.664	0.524	1.09	0.830	0.478	1.09	1.72
tmax (h)
Median (range)	0.50 (0.5–0.5)	0.50 (0.5–0.5)	0.37 (0.25–0.5)	1.00 (0.25–1)	0.50 (0.25–3)	1.00 (0.25–4)	0.50 (0.25–1)
CLR (l h−1)
Amean (n) (range)	0.117 (4) (0.0340–0.191)	0.0772 (3) (0.0129–0.182)	0.107 (5) (0.0320–0.213)	0.221 (6) (0.0425–0.425)	0.160 (7) (0.0137–0.851)	0.105 (9) (0.0134–0.178)	0.101 (7) (0.00864–0.343)
S.d.	0.0667	0.0918	0.0780	0.163	0.307	0.0526	0.110
fe (0–24) (%)
Amean (range)	0.0248 (4) (0.0121–0.0438)	0.0114 (3) (0.00512–0.0207)	0.0227 (5) (0.00907–0.0423)	0.0881 (6) (0.00430–0.224)	0.0222 (7) (0.00289–0.0712)	0.0231 (9) (0.00155–0.0704)	0.0375 (7) (0.00237–0.151)
S.d.	0.0135	0.00819	0.0123	0.0838	0.0259	0.0249	0.0516
	10 mg BID solution	20 mg BID solution	40 mg BID solution	40 mg BID tablet	60 mg BID tablet	90 mg BID tablet	120 mg BID tablet
Following BID dosing
Cmax ss (ng ml−1)
Gmean (n) (range)	17.3 (4) (11.6–29.1)	NC (2) (26.2–38.9)	61.9 (6) (48.7–81.4)	46.1 (5) (13.2–123)	82.8 (6) (14.6–596)	70.0 (4) (46.2–117)	355 (8) (124–650)
% CV	43.3	NC	19.5	69.9	130	44.1	44.4
AUCss (ng h ml−1)
Gmean (n) (range)	23.0 (4) (19.2–28.4)	NC (2) (47.0–74.6)	111 (6) (81.2–144)	101 (5) (44.1–271)	178 (6) (47.9–646)	122 (4) (55.3–197)	501 (7) (243–1760)
% CV	17.1	NC	22.5	72.3	87.5	51.4	85.3
Cmin ss (ng ml−1)
Gmean (n) (range)	0.114 (3) (0.057–0.189)	NC (1) (0.228–0.228)	0.370 (5) (0.162–0.821)	0.959 (5) (0.294–2.71)	1.47 ((6) (0.447–3.67)	0.543 (5) (0.177–3.18)	3.54 (5) (1.40–41.1)
% CV	52.1	NC	62.5	74.7	65.5	133	178
CLss/F (l h−1)
Amean (range)	439 (4) (352–521)	NC (2) (268–426)	369 (6) (278–492)	465 (5) (148–906)	483 (6) (92.9–1250)	856 (4) (457–1630)	283 (7) (68.2–494)
S.d.	72.9	NC	90.6	285	442	552	147
t1/2 ss (h)
Amean (range)	2.82 (3) (2.47–3.25)	NC (1) (1.70)	2.13 (4) (1.62–2.83)	3.04 (3) (2.65–3.70)	2.81 (4) (1.86–3.18)	2.63 (5) (1.89–3.16)	2.45 (6) (1.56–3.23)
S.d.	0.400	NC	0.539	0.570	0.636	0.514	0.549
tmax ss (h)
Median (range)	0.50 (4) (0.5–0.5)	NC (2) (0.25–1)	0.25 (6) (0.25–1)	1.00 (5) (0.5–1.5)	1.00 (6) (0.25–4)	0.50 (4) (0.5–3)	0.50 (8) (0.25–1.5)
R AC
Gmean (n) (range)	1.05 (4) (0.844–1.49)	NC (2) (1.64–2.07)	1.12 (6) (0.550–1.70)	0.817 (5) (0.447–1.18)	1.33 (6) (0.566–2.54)	1.20 (4) (0.834–1.71)	1.91 (7) (1.12–3.86)
% CV	28.0	NC	32.8	35.7	44.0	29.1	47.2
T c
Gmean (n) (range)	1.03 (4) (0.839–1.48)	NC (2) (1.61–2.07)	1.10 (6) (0.539–1.65)	0.806 (5) (0.444–1.13)	1.30 (6) (0.525–2.50)	1.18 (4) (0.831–1.69)	1.81 (7) (1.09–3.50)
% CV	28.3	NC	32.2	35.0	44.7	29.1	45.2

Abbreviations: A_mean=arithmetic mean; AUC=area under the plasma concentration–time curve from zero to infinity; AUC_ss=area under the plasma concentration–time curve over a dosing interval at steady state; AUC_0–12=area under the plasma concentration–time curve from zero to 12 h post dose; BID=twice-daily; C_max=maximum plasma concentration; C_{max ss}=maximum steady-state plasma concentration during dosing; C_{min ss}=minimum steady-state plasma concentration during dosing; CL/F=total apparent drug clearance; CL_R=renal clearance from plasma; CL_ss/F=total apparent drug clearance at steady state; f_{e (0–24)}=dose fraction excreted unchanged in the urine from zero to 24 h post dose; G_mean=geometric mean; NC=not calculated; R_AC=accumulation ratio; T_c=temporal change (linearity factor); t_max=time to maximum plasma concentration; t_{max ss}=time to maximum plasma concentration at steady state; t_1/2=half-life; t_{1/2 ss}=half-life at steady state; V_ss/F=steady-state volume of distribution; % CV=percentage confidence value.