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. 2020 Dec 1;3(1):fcaa211. doi: 10.1093/braincomms/fcaa211

Figure 6.

Figure 6

Pharmacokinetic (PK) studies of Epo and melatonin in the piglet. Previous pre-clinical studies identified the therapeutic target for Epo neuroprotection as: Cmax 6224–10 015 mU/ml and AUC48 117 677–140 000 U*h/l (Statler et al., 2007). Epo at 1000 u/kg (n = 3), 2000 u/kg (n = 1) and 3000 u/kg [with (n = 5) and without (n = 6) MEL 20 mg/kg)] was administered as an intravenous bolus at 1 h, 24 h and 48 h and Epo levels as maximum concentration (Cmax) (Mean ± SEM) (A) and total AUC levels over 48 h (AUC48) (B) are illustrated. Mean (±standard deviation) melatonin (MEL) plasma concentration (mg/l) for HT+MEL (n = 12) and HT+MEL+Epo (n = 12) treated animals are shown in C. The therapeutic level for MEL is likely between 15 mg/l and 30 mg/l based on our previous studies (Robertson et al., 2013, 2019, 2020).