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. 2019 Mar 23;8(3):280. doi: 10.3390/cells8030280

Figure 4.

Figure 4

Comparative Oral PK in Rats of MP101 (DNP) vs. MP201 (prodrug of DNP). Male Sprague-Dawley rats (weighing 250–300 g) were housed three per cage with ad libitum access to food and water in the Division of Laboratory Animal Resources, UAMS. Femoral vein-catheterized rats, were treated with MP201 at a single oral dose (N = 4/dose) of 8, 40 and 80 mg/kg (equivalent to 5, 25 and 50 mg/kg of MP101, respectively due to the extra molecular weight) or DNP at 5 mg/kg. Blood samples (0.15 mL) were collected at 0, 5, 15, 30, 45, 60, 120, 240 and 480 min. Plasma samples were prepared and analysis was run using LC/MS/MS spectrometry. (A) MP101 (DNP) at 5 mg/kg shows a quick rise and a high Cmax relative the same equivalent dose at 5 mg/kg of MP201 (adjusting for additional molecular weight). Data shown is MP201’s release of DNP upon cleavage of prodrug linker to an active form (MP101/DNP) with a ~20× suppression of Cmax compared to MP101. In addition, MP201 has a dose linear AUC going from 5 to 25 mg/kg. (B) In compensation for the lower Cmax relative to MP101, MP201 has a much longer elimination phase (~3×) extending the AUC significantly for a “trickle-like” effect delivering DNP (unpublished). *Below the limits of detection at 24-h time-point of 10 ng/mL.