Human Pharmacokinetics and Safety Profile of Finafloxacin, a New Fluoroquinolone Antibiotic, in Healthy Volunteers

DOI: 10.1128/AAC.00832-10

Article Figures & Data

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Fig. 1.
Dose proportionality of C_max after single-dose administration of finafloxacin.
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Fig. 2.
Dose proportionality of AUC_∞ after single-dose administration of finafloxacin.
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Fig. 3.
Arithmetic mean plus standard deviation of plasma finafloxacin concentration-versus-time profile on a logarithmic concentration scale in part A subjects.
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Fig. 4.
Arithmetic mean plus standard deviation of serum finafloxacin concentration-versus-time profile on a logarithmic concentration scale in part B subjects.

Table 1.

Demographic data

Subject group, dose regimen, and dose (mg)	Total no. of subjects	No. of male subjects	No. of female subjects	Mean body weight (kg)	Mean BMI (kg/m²)	Mean age (yr)
Part A, single dose
25	3	2	1	76.4	23.8	41.7
50	6	6	0	72.7	23.5	39.3
100	6	5	1	76.4	24.2	38.3
200	6	5	1	74.1	24.4	36.7
400	6	5	1	76.3	25.1	37.8
800	6	5	1	73.3	23.7	37.0
Placebo, single dose	10	7	3	72.1	23.9	44.4
Part B, 7 days q.d.
150	6	5	1	70.0	23.5	44.0
300	6	5	1	78.4	24.4	46.8
600	6	6	0	79.1	24.3	43.7
800	6	6	0	81.2	24.8	44.8
Placebo, multiple dose	8	7	1	79.6	25.7	42.3
Part C, 7 days q.d.
600	20	20	20	75.7	24.3	41.6

Table 2.

Plasma pharmacokinetics of finafloxacin in healthy volunteers after single-dose administration (part A)^{^a}

Dose (mg)	No. of subjects	C_max (mg/liter)	C_max,norm [(mg/liter)/mg]	AUC_∞ (h · mg/liter)	AUC_∞,norm [(h · mg/liter)/mg]	t_max (h)	t_1/2 (h)	CL/F (liters/h)	Vz/F (liters)
25	3	0.24	0.0096	0.42	0.017	1.00	1.28	59.0	109
50	6	0.44 ± 0.16	0.0088	1.26 ± 0.48	0.025	0.88	3.8 ± 2.7	45.0 ± 17.1	220 ± 127
100	6	1.32 ± 0.62	0.013	2.80 ± 0.72	0.028	0.50	7.2 ± 3.2	37.2 ± 7.5	389 ± 202
200	6	1.90 ± 0.73	0.0095	4.08 ± 1.05	0.020	0.75	4.6 ± 1.9	51.5 ± 11.7	348 ± 194
400	6	5.06 ± 2.09	0.013	14.2 ± 4.44	0.036	1.00	10.0 ± 4.4	30.8 ± 10.4	487 ± 363
800	6	11.1 ± 2.96	0.014	29.2 ± 7.50	0.036	0.88	10.5 ± 2.2	29.0 ± 7.7	435 ± 130

↵a Where indicated, values are means ± standard deviations. C_max, peak plasma concentration; AUC, area under the concentration-time curve; t_max, time to reach C_max (for this parameter median values are reported); t_1/2 terminal half life; CL/F, total body clearance; Vz/F, distribution volume based on the terminal phase; norm, values normalized by the administered dose per kg of body weight; AUC_∞, AUC extrapolated to infinite time.

Table 3.

Plasma pharmacokinetics of finafloxacin in six healthy volunteers per dose after multiple-dose administration (part B)^{^a}

Dose (mg)	Day no.	C_max (mg/liter)	C_max,norm [(mg/liter)/mg]	AUC_24h (h · mg/liter)	AUC_24h,norm [(h · mg/liter)/mg]	t_max (h)	t_1/2 (h)	CL/F (liters/h)	Vz/F (liters)
150	1	1.69 ± 0.38	0.011	3.76 ± 0.82	0.025	0.50
150	7	1.50 ± 0.52	0.010	4.01 ± 0.64	0.027	0.50	5.3 ± 0.6	37.4 ± 5.8	282 ± 25
300	1	2.96 ± 0.88	0.0099	8.75 ± 3.50	0.029	1.50
300	7	4.15 ± 2.11	0.014	9.09 ± 3.83	0.030	0.63	6.5 ± 2.5	37.4 ± 17.5	337 ± 155
600	1	7.67 ± 3.42	0.013	18.7 ± 7.63	0.031	0.75
600	7	6.76 ± 2.20	0.011	19.2 ± 6.40	0.032	0.88	8.8 ± 3.1	32.5 ± 10.2	409 ± 175
800	1	8.68 ± 1.96	0.011	20.8 ± 7.42	0.026	0.75
800	7	8.95 ± 3.11	0.011	26.1 ± 8.60	0.033	0.88	14.0 ± 5.5	31.6 ± 10.6	659 ± 467

↵a Where indicated, values are means ± standard deviations. AUC_24h, area under the plasma concentration-time curve to 24 h after dosing. For the explanation of other symbols, see the footnote to Table 2.

Table 4.

Finafloxacin concentrations in urine (part A)

Collection period (h)	Median finafloxacin concn (mg/liter [range]) at a dose of:
Collection period (h)	100 mg	200 mg	400 mg	800 mg
0–2	36.4 (16.5–101)	52.2 (30.6–159)	85.5 (50.8–134.0)	89.8 (38.0–242.0)
2–4	43.8 (19.3–61.9)	48.4 (34.9–166)	83.2 (44.7–328)	112.5 (62.6–193.0)
4–8	14.2 (6.3–36.5)	22.4 (11.9–91.7)	80.4 (29.4–207)	137.6 (43.9–257.0)
8–12	4.9 (1.1–6.9)	10.5 (2.0–31.5)	26.6 (9.3–63.9)	22.2 (12.1–87.1)
12–24	2.1 (0.7–4.8)	2.3 (0.9–13.0)	8.6 (5.0–11.3)	11.4 (7.5–54.0)
24–48	0.8 (0.1–1.1)	0.7 (0.5–1.6)	2.1 (1.4–7.5)	1.9 (0.7–73.8)

Table 5.

Urine pharmacokinetic parameters of finafloxacin after single-dose administration (part A)

Dose (mg)	No. of subjects	Recovery in urine (% of dose [range])	CL_R (liters/h)^{^a}
25	3	27.8 (27.0–29.2)	17.0 (10.5–19.2)
50	6	31.9 (25.8–38.1)	14.2 (10.8–17.5)
100	6	35.5 (26.8–44.1)	13.3 (10.1–16.5)
200	6	32.1 (19.3–44.9)	15.8 (12.8–18.8)
400	6	28.5 (20.0–37.0)	8.6 (4.9–12.2)
800	6	33.5 (26.1–40.8)	9.6 (7.5–11.6)

↵a Median (minimum-maximum) values are reported for the 25-mg dose; mean values (95% confidence limits) are reported for the other dose levels. CL_R, renal clearance.

Table 6.

AEs observed in the study parts

Subject group and dose (mg)	No. of subjects	No. (%) of subjects with AE	Total no. of AEs	No. of AEs per subject	No. of AEs by type^{^a}
Subject group and dose (mg)	No. of subjects	No. (%) of subjects with AE	Total no. of AEs	No. of AEs per subject	GI	NS	RTI	Other
Part A, single dose
25	3	1 (33)	3	0.33	1	1	0	1
50	6	0 (0)	0	0	0	0	0	0
100	6	2 (33)	3	0.5	0	1	0	2
200	6	5 (83)	7	1.17	1	4	0	2
400	6	1 (33)	2	0.33	1	1	0	0
800	6	5 (83)	11	1.83	2	1	0	8
Placebo, single dose	10	3 (33)	5	0.5	0	3	0	2
Part B, 7 days q.d.
150	6	4 (67)	13	2.17	1	3	1	8
300	6	0 (0)	0	0	0	0	0	0
600	6	3 (50)	5	0.83	3	1	0	1
800	6	5 (83)	10	1.67	1	1	1	7
Placebo, multiple dose	8	5 (63)	12	1.5	1	3	2	6
Part C
Fasting subjects	14	11 (79)	16	1.14	8	2	1	5
Fed subjects	6	4 (67)	10	1.67	5	2	0	3
Total group, 7 days q.d., 600 mg	20	15 (75)	26	1.30	13	4	1	8
Nonflatulence AE subjects		11 (55)	20	1.0	7	4	1	8

↵a GI, gastrointestinal; NS, nervous system; RTI, respiratory tract infections; Other, cardiovascular, musculoskeletal, eye, skin, local reaction at puncture site, and/or general.