. Author manuscript; available in PMC: 2019 Feb 1.

Published in final edited form as: Int J Tuberc Lung Dis. 2018 Aug 1;22(8):937–944. doi: 10.5588/ijtld.17.0515

Table 2.

Validation of the PBPK model for various anti-TB drugs against oral clinical formulations in adults

		Clinical			Simulated
Drug	Dose (mg)	C_max	C_trough	AUC	C_max	C_trough	AUC
Bedaquiline (single dose)¹⁴	10 mg	0.069 ± 0.015	-	^*1.248 ± 0.233	0.072 ± 0.011	-	^*1.421 ± 0.337
	30 mg	0.276 ± 0.064	-	^*4.418 ± 1.424	0.213 ± 0.038	-	^*4.226 ± 0.956
	100 mg	0.854 ± 0.283	-	^*13.604 ± 5.115	0.718 ± 0.126	-	^*14.117 ± 3.218
	300 mg	2.547 ± 1.305	-	^*38.737 ± 15.584	2.142 ± 0.359	-	^*42.063 ± 9.163
	450 mg	3.755 ± 1.165	-	^*64.530 ± 26.927	3.220 ± 0.545	-	^*62.687 ± 13.772
	700 mg	6.747 ± 2.210	-	^*97.816 ± 38.074	5.001 ± 0.784	-	^*98.131 ± 20.868

Delamanid (day 10)¹⁵	100 mg TID	0.606 ± 0.168	0.349 ± 0.049	^†11.8 ± 2.08	0.425 ± 0.119	0.276 ± 0.099	^†8.654 ± 2.638
	300 mg BD	0.512 ± 0.081	0.333 ± 0.068	^†10.2 ± 1.57	0.434 ± 0.121	0.222 ± 0.088	^†7.994 ± 2.467
	300 mg QD	0.412 ± 0.051	0.146 ± 0.041	^†5.84 ± 0.99	0.330 ± 0.085	0.093 ± 0.045	^†4.739 ± 1.421

Isoniazid (single dose)¹⁶	300 mg IA	6.77 ± 2.121	-	^‡14.24 ± 1.753	6.23 ± 1.31	-	^‡17.1 ± 6.59
	300 mg RA	5.72 ± 2.064	-	^‡9.54 ± 2.404	5.35 ± 1.16	-	^‡12.41 ± 4.53
	600 mg RA	13.92 ± 3.422	-	^‡24.99 ± 4.299	11.99 ± 2.53	-	^‡30.27 ± 9.89
	900 mg RA	21.49 ± 5.402	-	^‡48.19 ± 5.204	19.15 ± 4.17	-	^‡54.88 ± 18.17

Rifapentine (OD, day 14)¹⁷	5 mg/kg	15.7 (13.0–17.7)	-	^†218 (142-251)	13.2 (12.0-14.5)	6.7 (5.7-7.5)	^†237 (215-262)
	10 mg/kg	21.7 (21.3-22.2)	-	^†330 (284-340)	21.8 (19.9-23.8)	8.8 (7.4-10.0)	^†367 (326-397)
	15 mg/kg	35.9 (25.1-39.4)	-	^†560 (401-735)	37.8 (34.8-41.3)	22.9 (19.8- 25.3)	^†732 (664-803)
	20 mg/kg	34.1 (29.7-42.9)	-	^†483 (414-546)	35.6 (32.6-38.5)	14.9 (12.4- 16.8)	^†594 (540-644)

Values are represented as arithmetic mean ± standard deviation, Rifapentine clinical and simulated values are represented as median (IQR), AUC – area under the concentration-time curve, C_max – maximum plasma concentration, C_trough – trough plasma concentration at 24 h after administration; C_max and C_trough are expressed as mg/L and AUC is expressed as mg × h/L;

AUC_0-144,

^†

AUC_0-24,

^‡

AUC_0-12.

OD – once daily, BD – twice daily, TID – thrice daily.