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

Table 5 Pharmacokinetic non-compartmental results of rifampicin in children above and below 4 years of age

Rifampicin	<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)	9.38 (12.8)	10.2 (9.04)	p-value: 0.0002^a
C_MAX (ug/mL)	4.9	5.96	−17.8
T_MAX (hr)	2	3	−33.3
CL/F (L/hr)	4.66	7.86	−40.7
CL/F/BW (L/hr/kg)	0.52	0.41	26.8
V/F (L)	15.6	25.5	−38.9
V/F/BW (L/kg)	1.73	1.34	29.1
T_1/2 (hr)	2.31	2.25	2.67
AUC0-∞ (hr × ug/mL)	21.5	25.4	−15.7
AUC_0-∞/dosage (hr × ug/mL/(mg/kg))	2.36	2.6	−9.23
T > MIC (hr)	6.89	6.66	3.45
T > MIC/24 h (%)	28.7	27.8	3.39
AUC_{0–24 h} > MIC (hr × ug/mL)	11.7	14.7	−20.1

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