Developmental changes of fluconazole clearance in neonates and infants in relation to ontogeny of glomerular filtration rate: literature review and data analysis

Table 1 Pharmacokinetic parameters of fluconazole in neonates and infants

Reference	N	Country	PMA (weeks)	Dose (mg/kg)	Route	AUC_(0-∞) (μg・h/mL)	t_1/2 (h)	Vd (L/kg)	CL_BW (mL/min/kg)
Saxen et al. [14]	7	Finland	27 28 29^a	6	IV	NA	55.2-88.6	1.18–2.25	0.18–0.52
Krzeska et al. [15]	14	Poland	41–58	3	IV	42.3–156.0	10.7–41.8	0.76–2.60	0.32–1.18
Kondo et al. [16]	4	Japan	27–33	2	IV	NA	46.2–49.4	1.07–1.35	0.25–0.33
Seki et al. [17]	6	Japan	29–42	3	IV	56.7–90.9	31.6–52.6	0.57–1.01	NA
Piper et al. [18]	8	USA	39^b	25 (loading) 12 (maintenance)	IV	479.0^b 347-496^c	56^b 26-80^c	1.05^b 0.86–1.46^c	0.27^b 0.22–0.35^c
Wiest et al. [19]	1	USA	32	6	IV	NA	37.4	1.2	0.33
Fujii et al. [20]	6 1	Japan	40–44	3	IV PO	72.1^b 54.0	37.4^b 41.2	0.81^b 0.99	NA
Nahata et al. [21]	2^d 6	USA	30–43	6	IV PO	340.8, 425.3 340.5–636.1	NA	NA	0.16–0.29
Wenzl et al. [22]	2	Germany	36–56	4–6	PO	162.0–233.0	27.0–45.0	1.21–1.88	NA

N number of patients, PMA post-menstrual age, NA not available, AUC area under the curve, t_1/2 half-life, Vd volume of distribution, CL_BW clearance normalized to body weight
In the study of Saxen et al. [14], data were given as ranges of means for patients who received fluconazole at different PMA. In the studies of Fujii et al. [20] and Piper et al. [18], data were given as mean for individual groups. In the studies of Krzeska et al. [15], Kondo et al. [16], Seki et al. [17], Nahata et al. [21] and Wenzl et al. [22], data were given as ranges for individual patients’ values
^an = 4, ^bmean, ^cinterquartile range, ^dthe same patients were also studied in PO route

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