Table 5.

Relationship between benznidazole serum concentrations and appearance of ADRs

Time point (days)	Median benznidazole serum concn in μg/ml (IQR) [no. of patients] and associated P valuea
	Severe ADR			Skin symptoms			Fever			Pruritus			Gastrointestinal symptoms			Neurological/musculoskeletal symptoms
	No	Yes	P	No	Yes	P	No	Yes	P	No	Yes	P	No	Yes	P	No	Yes	P
15	6.4 (1.9) [41]	5.8 (3.1) [4]	0.6322	6.79 (2.31) [12]	6.38 (1.88) [33]	0.5046	6.4 (1.8) [40]	5.3 (0.7) [5]	0.1814	5.7 (2.3) [14]	6.4 (1.7) [31]	0.7499	6.7 (3.3) [10]	6.4 (1.8) [35]	0.4949	6.8 (1.5) [9]	6.0 (1.9) [36]	0.2171
30	6.1 (1.8) [41]	5.3 (1.8) [2]	0.4534	5.52 (1.45) [12]	6.20 (1.91) [31]	0.3572	6.1 (1.8) [39]	4.8 (3.5) [4]	0.2096	5.6 (1.8) [13]	6.1 (1.9) [30]	0.3023	6.2 (2.4) [11]	6.1 (1.8) [32]	0.3030	6.4(1.0) [10]	5.9 (1.8) [33]	0.4376
45	6.3 (1.9) [37]	4.8 (2.2) [2]	0.1613	6.16 (2.66) [12]	6.32 (2.51) [27]	0.5129	6.1 (2.2) [36]	7.5 (1.5) [3]	0.0651	7.1 (1.8) [11]	5.9 (2.1) [28]	0.0045b	6.3 (2.3) [9]	6.2 (1.9) [30]	0.8676	6.5(1.5) [9]	6.1 (2.4) [30]	0.3506
60	5.7 (1.7) [37]			5.78 (2.59) [12]	5.48 (1.59) [25]	0.9741	5.6 (1.7) [34]	6.8 (5.0) [3]	0.5043	6.1 (2.1) [10]	5.2 (2.3) [27]	0.7067	6.5 (1.6) [9]	5.2 (1.8) [28]	0.4054	6.5 (1.1) [9]	5.0 (2.1) [28]	0.0177

^aStatistical significance was set at P < 0.0125 (Wilcoxon rank sum test).

^bUncertain clinical significance due to the small number of cases compared.