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

Table 2 Pharmacokinetic non-compartmental results of pyrazinamide in children above and below 4 years of age

Pyrazinamide	<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)	4.70 (12.8)	5.12 (9.18)	p-value: 0.0001^a
C_MAX (ug/mL)	30.1	37.4	−19.5
T_MAX (hr)	2	3	−33.3
CL/F (L/hr)	1.09	1.88	−42
CL/F/BW (L/hr/kg)	0.12	0.1	20
V/F (L)	7.57	12.2	−37.9
V/F/BW (L/kg)	0.84	0.64	31.3
T_1/2 (hr)	4.82	4.5	7.11
AUC_0-∞ (hr × ug/mL)	245	284	−13.7
AUC_0-∞/dosage (hr × ug/mL/(mg/kg))	10.1	10.8	−6.2
T > MIC (hr)	7.28	8.46	−13.9
T > MIC/24 h (%)	30.3	35.2	−13.9
AUC > MIC (hr × ug/mL)	62.3	95.2	−34.6

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