Sheep THC Clearance and Distribution Estimates Depended on a Small Bioavailability Pilot
The sheep paper’s clearance and distribution estimates relied on an approximate oral-bioavailability value from a two-animal pilot. The numerical estimates should retain that assumption rather than being treated as independently established species constants.
The pilot supplied a limited reference
One sheep received intravenous THC and another oral THC. The paper describes limitations in the sampling available for the bioavailability calculation. That approximate estimate was then used in interpreting the larger oral pharmacokinetic study’s clearance and volume of distribution.
The assumed absorbed fraction affects derived values
After oral administration, the amount reaching systemic circulation is not simply the amount administered. Clearance and distribution calculations that depend on that fraction inherit uncertainty when it is only approximately known. Their reported precision cannot resolve uncertainty in an underlying assumption or the variability expected in a wider sheep population.
Cross-species numerical similarity is not validation
A value resembling a published human or other-species estimate does not demonstrate that the physiological processes are identical. Dose, route, protein binding and methods differ. The authors themselves emphasize that these sheep estimates are approximate. Their value is to characterize a preliminary ruminant model and guide further study, not to supply a precise clearance rule for every animal or a human cannabis detection calculation.
Related analysis: the study’s broader findings and limitations.
Research cited
Stevens and colleagues (2024). The Pharmacokinetics of Δ9-Tetrahydrocannabinol in Sheep.
