Study

Translatability of preclinical to early clinical tolerable and pharmacologically active dose ranges for central nervous system active drugs

2023 · primary-comparison · peer reviewed: yes · record 36859342 · PubMed

5 findings kept from this study. Each is one sentence comparing an animal with a human, extracted from the full text, checked against the located page, and adjudicated against the review's definition of an animal-versus-human comparison.

The preclinical data predicted the pharmacologically active range in humans to a high degree, with 18 out of 25 interventions showing an overlap of 80% or more for HED.

Concordant · level A · no species named · neurology · 60–83 percent · n 18/25

“Overall, the preclinical data predicted the pharmacologically active range in humans to a high degree, as indicated by an overlap of ≥ 80% in 18 out of 25 (72%) for HED, 15 out of 25 (60%) for Cmax and 19 out of 23 (83%) for AUC.”
page 8

The human upper tolerability range (HURAE) surpassed the NOAEL in 9 out of 25 studies for HED.

Discordant · level B · no species named · cross-cutting toxicology · 9 count · n 9/25

“For HED, the human upper tolerability range HURAE surpassed the NOAEL in 9 out of 25 studies (36%): IB2, IB3, IB4, IB6, IB8, IB9, IB11, IB14 and IB20 (Table 2, Fig. 3).”
page 4

The Cmax value of the HURAE surpassed the Cmax value of the NOAEL in 8 out of 25 studies.

Discordant · level B · no species named · cross-cutting toxicology · 8 count · n 8/25

“As shown in Table 2 and Fig. 3, the Cmax value of the HURAE surpassed the Cmax value of the NOAEL in 8 of the 25 studies (32%; IB2, IB4, IB5, IB6, IB8, IB10, IB15, and IB21).”
page 5

The HURAE surpassed the AUC associated with the NOAEL in 12 out of 23 studies.

Discordant · level B · no species named · cross-cutting toxicology · 12 count · n 12/23

“For AUC, Table 2 and Fig. 3 show that the HURAE surpassed the AUC associated with the NOAEL in 12 out of 23 studies (52%; IB2, IB4, IB5, IB6, IB8, IB15, IB16, IB18, IB20, IB21, IB23, IB25).”
page 5

The highest tolerated (administered) doses in humans (HURAE) were much lower than expected based on the NOAEL for all three exposure parameters in 4 out of 25 studies.

Discordant · level B · no species named · cross-cutting toxicology · 4 count · n 4/25

“In 4 out of 25 studies (24%), the highest tolerated (administered) doses in humans (HURAE) were much lower than expected based on the NOAEL for all three exposure parameters.”
page 9