Table 2. Pharmacokinetic parameters of AT13148.

The pharmacokinetic parameters between 5 - 300 mg in cycle 1. There was considerable variation of AUC and Cmax at doses of 160 mg and above.

Cycle 1		Tmax (h)	Cmax (nmol/L)	HL Lambda z (h)	AUClast (h*nmol/L)	* AUC to 48 h (h*nmol/L)	AUCINF obs (h*nmol/L)	Vz F obs (L)	Cl F obs (L/h)
Cohort 1 5mg	Mean	5	20	60	400	400	900	1400	20
	SD	5	15	27	21	210	350	290	11
	% CV	97	70.0	41	54	54	40	21	60
Cohort 2 10mg	Mean	6	15	40	300	300	600	1900	100
	SD	4.2	4.8	30	190	190	460	670	95
	% CV	75	32	85.0	66	66	77	36	96
Cohort 3 20mg	Mean	4	30	20	600	600	1000	2000	90
	SD	2.8	16	13	440	440	750	660	72
	% CV	66	46	56	70	70	78	32	83
Cohort 4 40mg	Mean	1.99	120	15	1900	1900	2100	1100	50
	SD	0.03	21	1.00	540	540	630	310	17
	% CV	2	18	7	29	29	30	28	33
Cohort 5 80mg	Mean	3	180	50	5000	5000	10000	1600	30
	SD	2	69	44	3000	3000	16000	910	22
	% CV	67	38	82	61	61	118	57	67
Cohort 6 160mg	Mean	5	400	40	12000	10000	20000	2000	40
	SD	2	290	22	7900	5900	16000	1300	28
	% CV	41	66	52	64	57	79	72	75
Cohort 7 240mg	Mean	5	500	40	15000	13000	30000	2000	50
	SD	2	280	17	9000	9000	24000	930	36
	% CV	40.0	61	44	63	70	94	48	80
Cohort 8 300mg	Mean	6.1	700	60	20000	20000	40000	1400	18
	SD	0.12	130	35	4100	4100	10000	600	4.8
	% CV	2	20	57	21	21	23	42	26
Cohort 10 180mg	Mean	4	400	40	13000	9000	20000	2000	50
	SD	2.3	190	21	8000	4700	14000	2200	59
	% CV	64	50	51	60	52	74	94	110