Table 4 Pharmacokinetic parameters

	1.25 mg kg ⁻¹	5 mg kg ⁻¹	10 mg kg ⁻¹	20 mg kg ⁻¹	30 mg kg ⁻¹
No. of patients	3	2	3	3	7
T _max (hours)
Mean (arithmetic)	4.03	1.07^a	2.12	1.12	2.8
Median	1.08	⁻	1.37	1.12	1.17
CV%	128	⁻	77.1	11.1	119
Max	10	⁻	4	1.25	9.88
Min	1	⁻	1	1	1
C_max (μ g ml⁻¹)
Mean (arithmetic)	31.6	88.5	231	593	758
Median	27.8	88.5	235	616	752
CV%	21.1	4.28	15.4	9.82	16
Max	39.2	91.1	265	637	974
Min	27.6	85.8	194	527	630
AUC (dayμg ml*⁻¹)
Mean (arithmetic)	319	882	1980	5020	6610
Median	327	882	1930	4960	6680
CV%	40	3.83	16.7	9.9	20.7
Max	442	906	2340	4960	8830
Min	188	858	1680	4550	4660
V_ss (ml kg⁻¹)
Mean (arithmetic)	53.5	100	71.2	47.3	59.2
Median	56.5	100	66.6	45.8	54.7
CV%	26.9	21	18.3	9.95	18.4
Max	66.1	115	85.9	52.6	71
Min	37.8	85.4	61	43.5	50.5
CL (ml day⁻¹ kg⁻¹)
Mean (arithmetic)	4.44	5.68	5.14	4.01	4.72
Median	3.83	5.68	5.18	4.03	4.49
CV%	44.8	3.83	16.3	9.77	21.5
Max	6.66	5.83	5.95	4.39	6.44
Min	2.83	5.52	4.28	3.61	3.4
t _1/2 (days)
Mean (arithmetic)	9.36	13.4	10.6	8.99	9.88
Median	9.41	13.4	10.5	8.52	9.08
CV%	32.7	28	19.1	9.54	28.8
Mean (geometric)	9.01	13.1	10.5	8.96	9.55
Mean (harmonic)	8.67	12.8	10.4	8.94	9.25
Max	12.4	16	12.7	9.98	14.7
Min	6.28	10.7	8.69	8.47	6.89
C_min (μg ml⁻¹)
Mean (arithmetic)	45^b	72^b	189^b	84^c	102^c
Median	35	83	164	81	108
CV%	81.6	30.9	30.3	7.97	26.1
Max	85.7	87.2	268	92	139
Min	14.5	46.7	135	79.6	69.1

Abbreviations: T_max=time of maximum concentration after intravenous infusion; C_max=maximum observed concentration after intravenous infusion; CV%=coefficient of variation; AUC=area under curve (the area under the concentration–time curve, from time zero to infinity); V_ss=volume of distribution at steady state; CL=plasma clearance; t_1/2=terminal half life
^aOne patient.
^bTrough concentration is calculated as the mean of individual concentrations before dose 8 (n=3).
^cTrough concentration is calculated as the mean of individual concentrations before dose 3 (n=3 for 20 mg kg⁻¹ and n=8 for 30 mg kg⁻¹).

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