FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Frontiers in veterinary science2025; 12; 1688214; doi: 10.3389/fvets.2025.1688214

Metabolism, pharmacokinetics, and bioavailability of cannabigerol in horses following intravenous and oral administration with micellar and oil formulations.

Abstract: Cannabigerol (CBG) is a non-psychoactive cannabinoid with growing interest in veterinary medicine; however, its pharmacokinetic profile in horses remains unknown. Understanding its absorption, distribution, metabolism, and elimination is essential to optimizing dosing strategies and evaluating its potential for clinical use in equine patients. Unassigned: A prospective crossover study was conducted in eight healthy adult horses to assess the metabolism and the pharmacokinetics after intravenous (IV) administration at 1 mg/kg and oral administrations at 10 mg/kg with two formulations (micellar and oil). Plasma concentrations of CBG and its main metabolite, CBG-glucuronide (CBG-G), were analyzed by LC-MSMS and modeled using a non-linear mixed effects model with MonolixSuite®. The model estimated the bioavailability, metabolic conversion, and absorption parameters. Furthermore, Monte Carlo simulations were performed to predict and evaluate the drug exposure after a multiple-dose regimen. Unassigned: High metabolism was observed with the formation of epoxy and hydroxy metabolites via phase I reactions, and CBG-G was the main metabolite from phase II reactions (75% of biotransformation). After IV administration, CBG showed a high volume of distribution (V = 74 L/kg) and systemic clearance (Cl = 1.67 L/h/kg), with a terminal half-life of approximately 29 h. The oral bioavailability was estimated at 28% between formulations, and an extensive presystemic metabolism was obtained with metabolite/parent AUC ratios exceeding 50. The micellar formulation showed a shorter time to achieve maximum concentration (T) and faster absorption as compared to the oil formulation. The Monte Carlo simulations of multiple oral doses (10 mg/kg q24 h for 14 days) predicted differences between formulations. No adverse clinical effects were observed during the study. Unassigned: This study shows the first evaluation of the metabolism and pharmacokinetics of CBG in horses after IV and oral administration. The findings highlight extensive metabolite formation with significant glucuronidation, a large distribution volume, and high clearance. While both oral formulations produced similar systemic exposure, the faster absorption with the micellar formulation may inform clinical decisions depending on therapeutic goals. These data support the potential use of CBG in horses and offer a foundation for further studies in equine medicine.
Copyright © 2025 Serrano-Rodríguez, Miraz, Saitua, Díez de Castro, Ledesma-Escobar, Ferreiro-Vera, Priego-Capote, Sánchez de Medina and Sánchez de Medina.
Get Full Text
Publication Date: 2025-10-29 PubMed ID: 41234397PubMed Central: PMC12607281DOI: 10.3389/fvets.2025.1688214Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigated how cannabigerol (CBG), a non-psychoactive cannabinoid, is absorbed, metabolized, distributed, and cleared in horses after intravenous and oral administration using two formulations (micellar and oil).
  • The research provided detailed pharmacokinetic data, including the bioavailability and metabolism of CBG, and evaluated its potential for clinical use in equine veterinary medicine.

Study Purpose and Importance

  • Cannabigerol (CBG) is gaining interest as a veterinary therapeutic agent, but its behavior in horses—such as how the drug is absorbed, metabolized, distributed, and eliminated—was previously unknown.
  • Understanding these pharmacokinetic properties is essential for developing effective dosing strategies and assessing CBG’s safety and efficacy in horses.

Methodology

  • A prospective crossover design was used with eight healthy adult horses to ensure each horse received all treatments, minimizing individual variability.
  • CBG was administered in two ways:
    • Intravenous (IV) injection at a dose of 1 mg/kg to assess direct systemic pharmacokinetics without absorption barriers.
    • Oral administration at 10 mg/kg using two different formulations: micellar and oil, to evaluate absorption differences and oral bioavailability.
  • Plasma concentrations of CBG and its main metabolite, CBG-glucuronide (CBG-G), were measured using advanced liquid chromatography-mass spectrometry (LC-MSMS) for accurate quantification.
  • Pharmacokinetic modeling was performed using a non-linear mixed effects model with MonolixSuite®, allowing estimation of key parameters such as bioavailability, absorption rates, metabolic conversion rates, volume of distribution, and clearance.
  • Monte Carlo simulations were conducted to predict the drug exposure after repeated oral dosing (10 mg/kg every 24 hours for 14 days), assessing steady-state pharmacokinetics and differences between formulations.

Main Findings: Metabolism

  • CBG underwent extensive metabolism in horses, primarily through two phases:
    • Phase I reactions: formation of epoxy and hydroxy metabolites.
    • Phase II reactions: dominant metabolite was CBG-glucuronide (CBG-G), which accounted for about 75% of total biotransformation, indicating significant glucuronidation.
  • The high metabolite formation suggested substantial presystemic metabolism, especially after oral administration.

Main Findings: Pharmacokinetics

  • After IV administration:
    • CBG showed a very high volume of distribution (74 L/kg), indicating widespread distribution into tissues beyond the blood plasma.
    • Systemic clearance was high (1.67 L/h/kg), reflecting rapid elimination from systemic circulation.
    • Terminal half-life was approximately 29 hours, suggesting relatively long persistence in the body after IV dosing.
  • After oral administration:
    • Oral bioavailability was about 28% for both micellar and oil formulations, implying moderate absorption but extensive first-pass metabolism.
    • The ratio of metabolite to parent drug AUC values exceeded 50, reinforcing the degree of presystemic metabolism.
    • The micellar formulation resulted in faster absorption and shorter time to reach maximum plasma concentration (Tmax) compared to the oil formulation.

Monte Carlo Simulations for Multiple Dosing

  • Simulated multiple-dose scenarios (10 mg/kg every 24 h for 14 days) predicted differences in drug exposure between micellar and oil formulations.
  • The faster absorption of the micellar formulation may lead to quicker onset of action, which could be beneficial depending on therapeutic goals.
  • These simulations help anticipate steady-state levels and guide dosing regimen design.

Safety Observations

  • No adverse clinical effects were observed during the study period for any administration route or formulation.
  • This suggests CBG is well tolerated in healthy adult horses at investigated doses.

Conclusions and Implications

  • This work represents the first comprehensive pharmacokinetic and metabolism evaluation of CBG in horses.
  • Key pharmacokinetic characteristics identified include:
    • Extensive metabolism primarily via glucuronidation (phase II).
    • Large distribution volume indicating wide tissue dissemination.
    • High systemic clearance resulting in substantial elimination capacity.
  • Oral bioavailability is moderate and similar between micellar and oil formulations, but micellar shows advantages in absorption speed.
  • Faster absorption via micellar formulations may be preferable in clinical situations requiring rapid effects, while both formulations achieve comparable overall exposure.
  • These findings establish a pharmacokinetic foundation to support potential therapeutic use of CBG in equine medicine and highlight areas for further investigation, such as efficacy trials or different dosing strategies.

Cite This Article

APA
Serrano-Rodríguez JM, Miraz R, Saitua A, Díez de Castro E, Ledesma-Escobar C, Ferreiro-Vera C, Priego-Capote F, Sánchez de Medina V, Sánchez de Medina A. (2025). Metabolism, pharmacokinetics, and bioavailability of cannabigerol in horses following intravenous and oral administration with micellar and oil formulations. Front Vet Sci, 12, 1688214. https://doi.org/10.3389/fvets.2025.1688214

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 12
Pages: 1688214
PII: 1688214

Researcher Affiliations

Serrano-Rodríguez, Juan Manuel
  • Pharmacology Area, Department of Nursing, Pharmacology and Physiotherapy, Veterinary Faculty, University of Córdoba, Córdoba, Spain.
Miraz, Raquel
  • Veterinary Clinical Hospital, University of Cordoba, Córdoba, Spain.
  • Department of Animal Medicine and Surgery, Veterinary Faculty, University of Cordoba, Córdoba, Spain.
  • Equine Sports Medicine Center CEMEDE, Department of Animal Medicine and Surgery, Veterinary Faculty, University of Córdoba, Córdoba, Spain.
Saitua, Aritz
  • Veterinary Clinical Hospital, University of Cordoba, Córdoba, Spain.
  • Equine Sports Medicine Center CEMEDE, Department of Animal Medicine and Surgery, Veterinary Faculty, University of Córdoba, Córdoba, Spain.
Díez de Castro, Elisa
  • Veterinary Clinical Hospital, University of Cordoba, Córdoba, Spain.
Ledesma-Escobar, Carlos
  • Department of Analytical Chemistry, Science Faculty, University of Córdoba, Córdoba, Spain.
  • Chemical Institute for Energy and Environment (IQUEMA), Campus of Rabanales, University of Córdoba, Córdoba, Spain.
Ferreiro-Vera, Carlos
  • Phytoplant Research S.L.U., Córdoba, Spain.
Priego-Capote, Feliciano
  • Department of Analytical Chemistry, Science Faculty, University of Córdoba, Córdoba, Spain.
Sánchez de Medina, Verónica
  • Phytoplant Research S.L.U., Córdoba, Spain.
Sánchez de Medina, Antonia
  • Veterinary Clinical Hospital, University of Cordoba, Córdoba, Spain.
  • Department of Animal Medicine and Surgery, Veterinary Faculty, University of Cordoba, Córdoba, Spain.
  • Equine Sports Medicine Center CEMEDE, Department of Animal Medicine and Surgery, Veterinary Faculty, University of Córdoba, Córdoba, Spain.

Conflict of Interest Statement

CF-V and VS are Phytoplant Research employees, manufacturers of cannabigerol, the drug investigated in this research. The Phytoplant Research S.L.U. company intends to apply for a patent related to the micellar formulation used in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 66 references
  1. Nachnani R, Raup-Konsavage WM, Vrana KE. The pharmacological case for Cannabigerol. J Pharmacol Exp Ther (2021) 376:204–12.
    doi: 10.1124/jpet.120.000340pubmed: 33168643google scholar: lookup
  2. Jastrząb A, Jarocka-Karpowicz I, Skrzydlewska E. The origin and biomedical relevance of Cannabigerol. Int J Mol Sci (2022) 23:7929.
    doi: 10.3390/ijms23147929pmc: PMC9322760pubmed: 35887277google scholar: lookup
  3. Navarro G, Varani K, Reyes-Resina I, Sánchez de Medina V, Rivas-Santisteban R, Sánchez-Carnerero Callado C. Cannabigerol action at cannabinoid CB and CB receptors and at CB-CB Heteroreceptor complexes. Front Pharmacol (2018) 9:632.
    doi: 10.3389/fphar.2018.00632pmc: PMC6021502pubmed: 29977202google scholar: lookup
  4. Svízenská I, Dubový P, Sulcová A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures--a short review. Pharmacol Biochem Behav (2008) 90:501–11.
    doi: 10.1016/j.pbb.2008.05.010pubmed: 18584858google scholar: lookup
  5. Ghovanloo MR, Dib-Hajj SD, Goodchild SJ, Ruben PC, Waxman SG. Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: an update on cannabidiol and cannabigerol. Front Physiol (2022) 13:1066455.
    doi: 10.3389/fphys.2022.1066455pmc: PMC9691960pubmed: 36439273google scholar: lookup
  6. Aqawi M, Sionov RV, Gallily R, Friedman M, Steinberg D. Anti-bacterial properties of cannabigerol toward . Front Microbiol (2021) 12:656471.
    doi: 10.3389/fmicb.2021.656471pmc: PMC8100047pubmed: 33967995google scholar: lookup
  7. Borrelli F, Fasolino I, Romano B, Capasso R, Maiello F, Coppola D. Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochem Pharmacol (2013) 85:1306–16.
    doi: 10.1016/j.bcp.2013.01.017pubmed: 23415610google scholar: lookup
  8. Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG. Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol (2010) 159:129–41.
    doi: 10.1111/j.1476-5381.2009.00515.xpmc: PMC2823359pubmed: 20002104google scholar: lookup
  9. Calapai F, Cardia L, Esposito E, Ammendolia I, Mondello C, Lo Giudice R. Pharmacological aspects and biological effects of Cannabigerol and its synthetic derivatives. Evid Based Complement Alternat Med (2022) 2022:1–14.
    doi: 10.1155/2022/3336516pmc: PMC9666035pubmed: 36397993google scholar: lookup
  10. Story G, Lee J, Cohen G, Rani A, Doherty J, Sela DA. Impact of dietary fat and Oral delivery system on Cannabigerol pharmacokinetics in adults. Cannabis Cannabinoid Res (2024) 9:1543–55.
    doi: 10.1089/can.2023.0174pmc: PMC11685294pubmed: 38574248google scholar: lookup
  11. Amstutz K, Schwark WS, Zakharov A, Gomez B, Lyubimov A, Ellis K. Single dose and chronic oral administration of cannabigerol and cannabigerolic acid-rich hemp extract in fed and fasted dogs: physiological effect and pharmacokinetic evaluation. J Vet Pharmacol Ther (2022) 45:245–54.
    doi: 10.1111/jvp.13048pubmed: 35246858google scholar: lookup
  12. Deiana S, Watanabe A, Yamasaki Y, Amada N, Arthur M, Fleming S. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour. Psychopharmacology (2012) 219:859–73.
    doi: 10.1007/s00213-011-2415-0pubmed: 21796370google scholar: lookup
  13. Aragona F, Tabbì M, Gugliandolo E, Giannetto C, D'Angelo F, Fazio F. Role of cannabidiolic acid or the combination of cannabigerol/cannabidiol in pain modulation and welfare improvement in horses with chronic osteoarthritis. Front Vet Sci (2024) 11:1496473.
    doi: 10.3389/fvets.2024.1496473pmc: PMC11668182pubmed: 39720409google scholar: lookup
  14. Harvey DJ, Brown NK. In vitro metabolism of cannabigerol in several mammalian species. Biomed Environ Mass Spectrom (1990) 19:545–53.
    doi: 10.1002/bms.1200190905pubmed: 2224182google scholar: lookup
  15. Havlasek J, Vrba J, Zatloukalova M, Papouskova B, Modriansky M, Storch J. Hepatic biotransformation of non-psychotropic phytocannabinoids and activity screening on cytochromes P450 and UDP-glucuronosyltransferases. Toxicol Appl Pharmacol (2023) 476:116654.
    doi: 10.1016/j.taap.2023.116654pubmed: 37574147google scholar: lookup
  16. Sánchez de Medina A, Serrano-Rodríguez JM, Díez de Castro E, García-Valverde MT, Saitua A, Becero M. Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations. Equine Vet J (2023) 55:1094–103.
    doi: 10.1111/evj.13923pubmed: 36624043google scholar: lookup
  17. Baggot JD. Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview. J Vet Pharmacol Ther (1992) 15:160–73.
    doi: 10.1111/j.1365-2885.1992.tb01003.xpubmed: 1433478google scholar: lookup
  18. Davis JL, Little D, Blikslager AT, Papich MG. Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary investigation. J Vet Pharmacol Ther (2006) 29:379–85.
    doi: 10.1111/j.1365-2885.2006.00757.xpubmed: 16958782google scholar: lookup
  19. Maxwell L. Horse of a different color: peculiarities of equine pharmacology. In: Maxwell L, editor. Equine pharmacology. 1st ed. Iowa, USA: John Wiley and Sons; (2015). 3–15.
  20. Martinez MN, Papich MG, Fahmy R. Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics. ADMET DMPK (2022) 10:1–25.
    doi: 10.5599/admet.1140pmc: PMC8963575pubmed: 35360673google scholar: lookup
  21. Song Y, Day CM, Afinjuomo F, Tan JE, Page SW, Garg S. Advanced strategies of drug delivery via oral, topical, and parenteral administration routes: where do equine medications stand?. Pharmaceutics (2023) 15:186.
    doi: 10.3390/pharmaceutics15010186pmc: PMC9861747pubmed: 36678815google scholar: lookup
  22. Bermingham E, Davis JL, Whittem T. Study design synopsis: designing and performing pharmacokinetic studies for systemically administered drugs in horses. Equine Vet J (2020) 52:643–50.
    doi: 10.1111/evj.13312pubmed: 32748990google scholar: lookup
  23. Wang Y, Jadhav PR, Lala M, Gobburu JV. Clarification on precision criteria to derive sample size when designing pediatric pharmacokinetic studies. J Clin Pharmacol (2012) 52:1601–6.
    doi: 10.1177/0091270011422812pubmed: 22162537google scholar: lookup
  24. Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst Pharmacol (2013) 2:e38.
    doi: 10.1038/psp.2013.14pmc: PMC3636497pubmed: 23887688google scholar: lookup
  25. Jusko WJ. Perspectives on variability in pharmacokinetics of an oral contraceptive product. Contraception (2017) 95:5–9.
    doi: 10.1016/j.contraception.2016.07.019pmc: PMC5422991pubmed: 27475034google scholar: lookup
  26. Ledesma-Escobar CA, Priego-Capote F, Calderón-Santiago M. Metabomsdia: a tool for implementing data-independent acquisition in metabolomic-based mass spectrometry analysis. Anal Chim Acta (2023) 1266:341308.
    doi: 10.1016/j.aca.2023.341308pubmed: 37244659google scholar: lookup
  27. Pelligand L, Soubret A, King JN, Elliott J, Mochel JP. Modeling of large pharmacokinetic data using nonlinear mixed-effects: a paradigm shift in veterinary pharmacology. A case study with Robenacoxib in cats. CPT Pharmacometrics Syst Pharmacol (2016) 5:625–35.
    doi: 10.1002/psp4.12141pmc: PMC5193001pubmed: 27770596google scholar: lookup
  28. Ayral G, Si Abdallah JF, Magnard C, Chauvin J. A novel method based on unbiased correlations tests for covariate selection in nonlinear mixed effects models: the COSSAC approach. CPT Pharmacometrics Syst Pharmacol (2021) 10:318–29.
    doi: 10.1002/psp4.12612pmc: PMC8099437pubmed: 33755345google scholar: lookup
  29. Goutelle S, Woillard JB, Neely M, Yamada W, Bourguignon L. Nonparametric methods in population pharmacokinetics. J Clin Pharmacol (2022) 62:142–57.
    doi: 10.1002/jcph.1650pubmed: 33103785google scholar: lookup
  30. Serrano-Rodríguez JM, Fernández-Varón E, Rodríguez CMC, Andrés-Larrea MIS, Rubio-Langre S, de la Fe C. Population pharmacokinetics and pharmacokinetic/pharmacodynamic evaluation of marbofloxacin against coagulase-negative staphylococci, Staphylococcus aureus and pathogens in goats. Res Vet Sci (2023) 159:1–10.
    doi: 10.1016/j.rvsc.2023.03.026pubmed: 37060837google scholar: lookup
  31. Granados MM, Medina-Bautista F, Navarrete-Calvo R, Argüelles D, Domínguez-Pérez JM, Priego-Capote F. Population pharmacokinetics and clinical evaluation of intravenous acetaminophen and its metabolites in Andalusian horses. Vet J (2025) 312:106357.
    doi: 10.1016/j.tvjl.2025.106357pubmed: 40286979google scholar: lookup
  32. Schoemaker RC, Cohen AF. Estimating impossible curves using NONMEM. Br J Clin Pharmacol (1996) 42:283–90.
    doi: 10.1046/j.1365-2125.1996.04231.xpmc: PMC2042675pubmed: 8877017google scholar: lookup
  33. Bon C, Toutain PL, Concordet D, Gehring R, Martin-Jimenez T, Smith J. Mathematical modeling and simulation in animal health. Part III: using nonlinear mixed-effects to characterize and quantify variability in drug pharmacokinetics. J Vet Pharmacol Ther (2018) 41:171–83.
    doi: 10.1111/jvp.12473pubmed: 29226975google scholar: lookup
  34. Zhou H. Pharmacokinetic strategies in deciphering atypical drug absorption profiles. J Clin Pharmacol (2003) 43:211–27.
    doi: 10.1177/0091270002250613pubmed: 12638389google scholar: lookup
  35. Gusson F, Carletti M, Albo AG, Dacasto M, Nebbia C. Comparison of hydrolytic and conjugative biotransformation pathways in horse, cattle, pig, broiler chick, rabbit and rat liver subcellullar fractions. Vet Res Commun (2006) 30:271–83.
    doi: 10.1007/s11259-006-3247-ypubmed: 16437303google scholar: lookup
  36. Di Salvo A, Chiaradia E, Sforna M, Della Rocca G. Endocannabinoid system and phytocannabinoids in the main species of veterinary interest: a comparative review. Vet Res Commun (2024) 48:2915–41.
    doi: 10.1007/s11259-024-10509-7pmc: PMC11442603pubmed: 39162768google scholar: lookup
  37. Harvey DJ, Brown NK. Comparative in vitro metabolism of the cannabinoids. Pharmacol Biochem Behav (1991) 40:533–40.
    doi: 10.1016/0091-3057(91)90359-apubmed: 1806943google scholar: lookup
  38. Roy P, Dennis DG, Eschbach MD, Anand SD, Xu F, Maturano J. Metabolites of cannabigerol generated by human cytochrome P450s are bioactive. Biochemistry (2022) 61:2398–408.
    doi: 10.1021/acs.biochem.2c00383pmc: PMC10337483pubmed: 36223199google scholar: lookup
  39. Ferlini Agne G, Somogyi AA, Sykes B, Knych H, Franklin S. Identification and kinetics of microsomal and recombinant equine liver cytochrome P450 enzymes responsible for in vitro metabolism of omeprazole. Biochem Pharmacol (2023) 214:115635.
    doi: 10.1016/j.bcp.2023.115635pubmed: 37285945google scholar: lookup
  40. Corado CR, McKemie DS, Knych HK. Dextromethorphan and debrisoquine metabolism and polymorphism of the gene for cytochrome P450 isozyme 2D50 in thoroughbreds. Am J Vet Res (2016) 77:1029–35.
    doi: 10.2460/ajvr.77.9.1029pubmed: 27580115google scholar: lookup
  41. Hamamoto-Hardman BD, Baden RW, McKemie DS, Knych HK. Equine uridine diphospho-glucuronosyltransferase 1A1, 2A1, 2B4, 2B31: cDNA cloning, expression and initial characterization of morphine metabolism. Vet Anaesth Analg (2020) 47:763–72.
    doi: 10.1016/j.vaa.2020.07.033pubmed: 32933848google scholar: lookup
  42. Toutain PL, Bousquet-Mélou A. Volumes of distribution. J Vet Pharmacol Ther (2004) 27:441–53.
    doi: 10.1111/j.1365-2885.2004.00602.xpubmed: 15601439google scholar: lookup
  43. Smith DA, Beaumont K, Maurer TS, Di L. Volume of distribution in drug design. J Med Chem (2015) 58:5691–8.
    doi: 10.1021/acs.jmedchem.5b00201pubmed: 25799158google scholar: lookup
  44. De Backer P, Vandecasteele-Thienpont LM, Jonckheere JA, Belpaire FM, Debackere M, de Leenheer AP. Bioavailability of bromhexine in the horse. Zentralbl Veterinarmed A (1980) 27:740–5.
    doi: 10.1111/j.1439-0442.1980.tb02026.xpubmed: 6784404google scholar: lookup
  45. De Clercq D, Baert K, Croubels S, van Loon G, Maes A, Tavernier R. Evaluation of the pharmacokinetics and bioavailability of intravenously and orally administered amiodarone in horses. Am J Vet Res (2006) 67:448–54.
    doi: 10.2460/ajvr.67.3.448pubmed: 16506906google scholar: lookup
  46. Wang TC, Wakshlag JJ, Jager MC, Schwark WS, Trottier NL, Chevalier JM. Chronic oral dosing of cannabidiol and cannabidiolic acid full-spectrum hemp oil extracts has no adverse effects in horses: a pharmacokinetic and safety study. Am J Vet Res (2025) 86:1–10.
    doi: 10.2460/ajvr.24.08.0235pubmed: 39787699google scholar: lookup
  47. Eichler F, Poźniak B, Machnik M, Schenk I, Wingender A, Baudisch N. Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses. Front Vet Sci (2023) 10:1234551.
    doi: 10.3389/fvets.2023.1234551pmc: PMC10445762pubmed: 37621871google scholar: lookup
  48. Toutain PL, Bousquet-Mélou A. Plasma clearance. J Vet Pharmacol Ther (2004) 27:415–25.
    doi: 10.1111/j.1365-2885.2004.00605.xpubmed: 15601437google scholar: lookup
  49. Newmeyer MN, Swortwood MJ, Barnes AJ, Abulseoud OA, Scheidweiler KB, Huestis MA. Free and glucuronide whole blood cannabinoids' pharmacokinetics after controlled smoked, vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: identification of recent Cannabis intake. Clin Chem (2016) 62:1579–92.
    doi: 10.1373/clinchem.2016.263475pubmed: 27899456google scholar: lookup
  50. Rague JM, Ma M, Dooley G, Wang GS, Friedman K, Henthorn TK. The minor cannabinoid cannabigerol (CBG) is a highly specific blood biomarker of recent cannabis smoking. Clin Toxicol (Phila) (2023) 61:363–9.
    doi: 10.1080/15563650.2023.2173076pmc: PMC10428941pubmed: 36939145google scholar: lookup
  51. Toutain PL. Why the racing industry and equestrian disciplines need to implement population pharmacokinetics: to learn, explain, summarize, harmonize, and individualize. Drug Test Anal (2025) 17:250–8.
    doi: 10.1002/dta.3706pmc: PMC11842173pubmed: 38685692google scholar: lookup
  52. Scarth JP, Teale P, Kuuranne T. Drug metabolism in the horse: a review. Drug Test Anal (2011) 3:19–53.
    doi: 10.1002/dta.174pubmed: 20967889google scholar: lookup
  53. Riviere JE, Gabrielsson J, Fink M, Mochel J. Mathematical modeling and simulation in animal health. Part I: moving beyond pharmacokinetics. J Vet Pharmacol Ther (2016) 39:213–23.
    doi: 10.1111/jvp.12278pubmed: 26592724google scholar: lookup
  54. Toutain PL, Bousquet-Mélou A. Plasma terminal half-life. J Vet Pharmacol Ther (2004) 27:427–39.
    doi: 10.1111/j.1365-2885.2004.00600.xpubmed: 15601438google scholar: lookup
  55. Turner SE, Knych HK, Adams AA. Pharmacokinetics of cannabidiol in a randomized crossover trial in senior horses. Am J Vet Res (2022) 83:28.
    doi: 10.2460/ajvr.22.02.0028pubmed: 35895770google scholar: lookup
  56. Stella B, Baratta F, Della Pepa C, Arpicco S, Gastaldi D, Dosio F. Cannabinoid formulations and delivery systems: current and future options to treat pain. Drugs (2021) 81:1513–57.
    doi: 10.1007/s40265-021-01579-xpmc: PMC8417625pubmed: 34480749google scholar: lookup
  57. Gaucher G, Satturwar P, Jones MC, Furtos A, Leroux JC. Polymeric micelles for oral drug delivery. Eur J Pharm Biopharm (2010) 76:147–58.
    doi: 10.1016/j.ejpb.2010.06.007pubmed: 20600891google scholar: lookup
  58. Anderson LL, Etchart MG, Bahceci D, Golembiewski TA, Arnold JC. Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations. Sci Rep (2021) 11:14948.
    doi: 10.1038/s41598-021-94212-6pmc: PMC8298633pubmed: 34294753google scholar: lookup
  59. Equine RB. Drug transporters: a mini-review and veterinary perspective. Pharmaceutics (2020) 12:1064.
    doi: 10.3390/pharmaceutics12111064pmc: PMC7695171pubmed: 33171593google scholar: lookup
  60. Piotrovskii VK. The use of Weibull distribution to describe the in vivo absorption kinetics. J Pharmacokinet Biopharm (1987) 15:681–6.
    doi: 10.1007/BF01068420pubmed: 3450849google scholar: lookup
  61. Higaki K, Choe SY, Löbenberg R, Welage LS, Amidon GL. Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans. Eur J Pharm Biopharm (2008) 70:313–25.
    doi: 10.1016/j.ejpb.2008.02.022pubmed: 18434110google scholar: lookup
  62. Little TJ, Russo A, Meyer JH, Horowitz M, Smyth DR, Bellon M. Free fatty acids have more potent effects on gastric emptying, gut hormones, and appetite than triacylglycerides. Gastroenterology (2007) 133:1124–31.
    doi: 10.1053/j.gastro.2007.06.060pubmed: 17919488google scholar: lookup
  63. Martinez MN, Gehring R, Mochel JP, Pade D, Pelligand L. Population variability in animal health: influence on dose-exposure-response relationships: part II: modelling and simulation. J Vet Pharmacol Ther (2018) 41:E68–76.
    doi: 10.1111/jvp.12666pubmed: 29806231google scholar: lookup
  64. Tam VH, Kabbara S, Yeh RF, Leary RH. Impact of sample size on the performance of multiple-model pharmacokinetic simulations. Antimicrob Agents Chemother (2006) 50:3950–2.
    doi: 10.1128/AAC.00337-06pmc: PMC1635223pubmed: 16954312google scholar: lookup
  65. Franco V, Gershkovich P, Perucca E, Bialer M. The interplay between liver first-pass effect and lymphatic absorption of Cannabidiol and its implications for Cannabidiol Oral formulations. Clin Pharmacokinet (2020) 59:1493–500.
    doi: 10.1007/s40262-020-00931-wpubmed: 32785853google scholar: lookup
  66. Tian Y, Mao S. Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs. Expert Opin Drug Deliv (2012) 9:687–700.
    doi: 10.1517/17425247.2012.681299pubmed: 22519507google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,850 horse owners like you who receive our email updates on horse health and nutrition.