<i>In vivo</i> pharmacokinetics and tissue distribution profile of a Wnt/β-catenin pathway-targeting anticancer cassane diterpene isolated from <i>Caesalpinia pulcherrima</i>

A cassane diterpene, 6β-cinnamoyl-7α-hydroxyvouacapen-5α-ol (6βCHV), isolated from Caesalpinia pulcherrima , has emerged as a promising anticancer drug lead with reported Wnt/β-catenin pathway inhibitory activity and in vivo safety. The present study reports the in vivo pharmacokinetics and tissue distribution of 6βCHV in Wistar rats following a single oral dose of 200 mg/kg. A reproducible RP-HPLC-UV method was developed and validated for quantifying 6βCHV in rat plasma and tissues. Chromatographic separation was achieved using a gradient elution of methanol and water. The method was subsequently applied to investigate the pharmacokinetics and tissue distribution of 6βCHV. Plasma pharmacokinetic analysis revealed delayed and moderate absorption, with a T max of 4 h and a C max of 1314.12 ng/mL. Following absorption, 6βCHV is distributed widely across peripheral tissues, including the liver, heart, lungs, spleen, and kidneys, as well as pharmacological sanctuary sites such as the brain and testes. The highest concentrations were observed in the stomach, small intestine, and liver, with detectable levels persisting up to 24 h, reflecting extensive tissue partitioning and retention. Overall, these findings demonstrate that oral administration of 6βCHV is feasible. However, the delayed absorption suggests that further optimization of formulation or alternative administration routes may enhance systemic exposure. This study provides the first comprehensive pharmacokinetic and tissue distribution profile of 6βCHV, supporting its continued preclinical development as a potential anticancer therapeutic.