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

Table 4 Pharmacokinetic non-compartmental results of isoniazid in fast and slow acetylators

Isoniazid	SLOW	FAST	% difference
Number of patients enrolled^a	28	64
Body Weight (median kg - range)	10.0 (4.5–26.0)	13.0 (4.4–44.0)
Age (median months - range)	36 (6–180)	42 (2–180)
Dosage (mean - % CV)	4.82 (11.7)	4.70 (13.3)	p-value: > 0.05^b
C_MAX (ug/mL)	4.56	4.62	−1.3
T_MAX (hr)	1	2	−50
CL/F (L/hr)	2.28	2.47	−7.69
CL/F/BW (L/hr/kg)	0.23	0.19	21.1
V/F (L)	12.2	7.05	72.3
V/F/BW (L/kg)	1.21	0.54	124
T_1/2 (hr)	3.69	1.98	86.4
AUC0-∞ (hr × ug/mL)	21.9	22.8	−3.78
AUC_0-∞/dosage (hr × ug/mL/(mg/kg))	4.38	4.95	−11.5
T > MIC (hr)	14.8	11.9	24.7
T > MIC/24 h (%)	61.7	49.4	24.8
AUC_{0–24 h} > MIC (hr × ug/mL)	17.7	19.8	−10.7

^aAcetylator genotype was determined in 92 patients. ^bMann–Whitney T-test. 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

ISSN: 1471-2334