Table 2.
Results of PK studies of CO prodrugs
| Compound | t1/2 (h) in plasma | COHb peak (%) | Time to Peak (h) | COHb AUC (%·h) p.o. (25 mg/kg) | Oral absorption of intact CO prodrugs | Oral absorption of byproduct | CO delivery efficiency (%) |
||
|---|---|---|---|---|---|---|---|---|---|
| i.v. | i.p. | p.o. | |||||||
| CO-103 | 1.3 | 3.5 | 1 | 4.1 ± 0.3 | + | ++ | 100 | 3.7 | 11.7 |
| CO-125 | 1.6 | 3.2 | 1 | 6.1 ± 1.4 | + | + | |||
| CO-116 | 1.5 | 4.1 | 1 | 5.6 ± 1.1 | − | ++ | |||
| CO-104 | 6.0 | 2.6 | 1 | 2.3 ± 0.4 | ++ | + | |||
| CO-115 | 5.1 | 3.5 | 1 | + | |||||
Compounds ranked by their CO release rate. t1/2: release half-life of CO prodrug in SIF (50% DMSO); COHb AUC: area under the curve for blood COHb level subtracting the pre-administration baseline from time zero to the last sampling time point. Results are presented as the mean ± SD (n ≥ 3). CO delivery efficiency: ratio of COHb AUC of a given route over i.v. administration using i.v. result as 100%. Qualitative criteria: -: lower than detection limit; +: 0-2.5 μM·h; ++: >2.5 μM·h. As a comparison, i.v. dose of 25 mg/kg should give an AUC of 25 μM·h.