Naïve-pooled pharmacokinetic analysis of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of Vietnamese children with tuberculous meningitis

Table 3 Pharmacokinetic non-compartmental results of isoniazid in children above and below 4 years of age

Isoniazid	<4 years old	>4 years old	% difference
Number of patients enrolled	64	36
Body Weight (median kg - range)	9.0 (4.0–15.0)	19.0 (13.5–43.0)
Age (median months - range)	12 (2–48)	96 (48–180)
Dosage (mean - % CV)	25.0 (12.8)	27.3 (9.17)	p-value: 0.0002^a
C_MAX (ug/mL)	4.38	5.11	−14.3
T_MAX (hr)	2	3	−33.3
CL/F (L/hr)	2.48	3.88	−36.1
CL/F/BW (L/hr/kg)	0.28	0.2	40
V/F (L)	11.3	14.9	−23.8
V/F/BW (L/kg)	1.26	0.78	61.5
T_1/2 (hr)	3.17	2.66	19.2
AUC0-∞ (hr × ug/mL)	20.2	25.8	−21.8
AUC_0-∞/dosage (hr × ug/mL/(mg/kg))	4.48	5.26	−14.8
T > MIC (hr)	14.2	14.5	−1.8
T > MIC/24 h (%)	59.3	60.3	−1.79
AUC_{0–24 h} > MIC (hr × ug/mL)	16.3	22	−25.8

Apart for dosage with mean and % CV, all values are reported as median (range) or as median estimates for pharmacokinetic parameters. C _MAX maximum observed plasma concentration after oral administration, T _MAX observed time to reach C_MAX, CL/F oral elimination clearance, CL/F/BW elimination clearance corrected by the median body weight, V/F apparent volume of distribution, V/F/BW apparent volume of distribution corrected by the median body weight, T _1/2 terminal elimination half-life, AUC _0-∞ predicted area under the plasma concentration-time curve after the last dose from zero time to infinity, T > MIC time above the minimum inhibitory concentration, T > MIC/24 h percentage of the time above the minimum inhibitory concentration over the 24 h dose interval, AUC > MIC observed area under the plasma concentration-time curve above the minimum inhibitory concentration. % difference is calculated with the > 4 years group used as the reference. ^aMann–Whitney T-test

ISSN: 1471-2334