. 2022 May 31;11(8):1029–1044. doi: 10.1002/psp4.12811

TABLE 1.

Simulated scenarios and R ² for the evaluation of the predictivity of PK/PD indices for in vivo efficacy

Purposes of the scenarios	Scenario	In vitro and in vivo parameters							R ²
Purposes of the scenarios	Scenario	γ _vitro	γ _vivo	EC50_vitro (ng/mL)	EC50_vivo (ng/mL)	Emax_vivo (1/h)	Therapy duration (days)	Start of treatment (day) ^a	AUC₂₄	C _max	T _EC50	T _EC90	AUEC₂₄
Base scenario and its variations
Base scenario	1	1	1	24	24	1.5	10	7	0.88	0.49	0.22	<0	0.96
Importance of appropriate dose range	2	1	1	2.4	2.4	1.5	10	7	0.36	<0	0.79	<0	0.76
	3	1	1	7.2	7.2	1.5	10	7	0.64	0.06	<0	<0	0.89
	4	1	1	72	72	1.5	10	7	0.87	0.65	0.34	<0	0.92
	5	1	1	240	240	1.5	10	7	0.70	0.46	<0	<0	0.83
Mismatch between in vitro/in vivo drug potency	6	1	1	2.4	24	1.5	10	7	0.88	0.49	0.34	0.19	0.84
	7	1	1	7.2	24	1.5	10	7	0.88	0.49	0.92	<0	0.92
	8	1	1	72	24	1.5	10	7	0.88	0.49	<0	<0	0.93
	9	1	1	240	24	1.5	10	7	0.88	0.49	<0	<0	0.90
Impact of steepness of concentration‐effect curve	10	0.5	0.5	24	24	1.5	10	7	0.75	0.29	<0	<0	0.93
	11	0.7	0.7	24	24	1.5	10	7	0.89	0.54	<0	<0	0.97
	12	1.5	1.5	24	24	1.5	10	7	0.89	0.66	0.18	<0	0.91
	13	2	2	24	24	1.5	10	7	0.91	0.71	0.61	<0	0.90
Mismatch between in vitro/in vivo steepness of concentration‐effect curve	14	0.5	1	24	24	1.5	10	7	0.88	0.49	0.22	<0	0.94
	15	0.7	1	24	24	1.5	10	7	0.88	0.49	0.22	<0	0.91
	16	1.5	1	24	24	1.5	10	7	0.88	0.49	0.22	<0	0.91
	17	2	1	24	24	1.5	10	7	0.88	0.49	0.22	<0	0.87
Additional conditions
Impact of degree of in vivo drug efficacy	–	1	1	24	24	1	10	7	0.85	0.55	0.84	<0	0.91
	–	1	1	24	24	0.6	10	7	0.81	0.46	0.78	<0	0.88
	–	1	1	24	24	0.45	10	7	0.71	0.03	0.09	<0	0.78
Early stage vs. late stage of infection	–	1	1	24	24	1.5	10	3	0.93	0.54	<0	<0	0.98
Evaluation of shorter treatment duration	–	1	1	24	24	1.5	6	7	0.89	0.53	0.53	<0	0.96
	–	1	1	24	24	1.5	4	7	0.89	0.67	0.75	<0	0.95
	–	1	1	24	24	1.5	2	7	0.85	0.63	0.83	<0	0.95

Abbreviations: AUC, area under the curve; AUEC, area under the effect curve; EC50, concentration leading to half of the maximum effect; EC90, concentration leading to 90% of maximum effect; Emax, maximum effect; PK/PD, pharmacokinetic/pharmacodynamic.

^{^a}

Day after inoculum.