TABLE 3.
Pharmacokinetics of cannabinoids in animal models (avant).
| Rats | Guinea pigs | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Measured Compounds | THC, 11-OH-THC, THC-COOH, CBD, CBDV, THCV and CBG | THC, CBD, 11-OH-THC, THC-COOH | ||||||||
| Matrices | Plasma | Urine | Maternal and fetal plasma | Plasma | ||||||
| Mode of administration | Oral | Intravenous | Intranasal | Pulmonary | Subcutaneous | Intraperitoneal | Oral | Intravenous | Transdermal | |
| Cmax (ng/ml) | 39–3,200 (CBD) 5.5–3,200 (THC) 43 (THC-COOH) 20 (11-OH-THC) 2,200 (CBDV) 210 (THCV) 1,050 (CBG) | 3,596–12,917 (CBD) 194–20,620 ng/ml (THC), 10 ng/ml (11-OH-THC), 6 ng/ml (THC-COOH) | 19.9–35.4 (CBD) 49–66 (THC) | 230–330 (CBD) 11–300 (THC) 3.2 (THC-COOH) | 45–70 (CBD) 25–100 (THC) 5–10 (11-OH-THC) 11.9 (THC-COOH) | 2,400–2,600 (CBD) 1,300 (CBDV) 400 (THCV) 810 (CBG) | 8.5–9.3 (11-OH-THC) 18.4–22 (THC-COOH) | Maternal: 99–304 (THC) Fetal: 10–41 (THC) | 269 (CBD) 197.7 (THC) | 8.6–35.6 (CBD) |
| Tmax (hours) | 1–8 (CBD) 0.7–6 (THC) 8 (THC-COOH) 1–2 (11-OH-THC) 0.5 (CBDV, CBG) 2 (THCV) | 0.3–0.5 (CBD) 1.5–1.6 (THC) | 0–15 min (CBD) 0–10 min (THC) 8 h (THC-COOH) | 1 (CBD, THC, 11-OH-THC) 4 (THC-COOH) | 0.5–2 (CBD) 4 (CBDV) 0.5 (THCV) 1 (CBG) | Maternal and fetal: 1 h (THC) (not Tmax) | 31.2–38.4 (CBD) | |||
| Half-life (hours) | 1.8–4.6 (CBD) 4.0 (CBDV) 1.5 (THCV) 1.7 (CBG) | 1.1–1.4 (CBD) 1.3 (THC) | 1.2–2.8 (CBD) | 3.7 (THC) | 7.8–10.1 (CBD) 6.7 (CBDV) 10 (THCV) 9.3 (CBG) | 3.5 (CBD) | ||||
| Time of sampling | 0–24 h after administration | 0–48 h after administration | ||||||||
| Articles | Pryor et al. (1977); Hutchings et al. (1989); Valiveti and Stinchcomb, (2004); Valiveti et al. (2007); Paudel et al. (2010); Deiana et al. (2012); Zgair et al. (2015); Cherniakov et al. (2017b); Hlozek et al. (2017); Ravula et al. (2018); Fuchs et al. (2019); Izgelov et al. (2020a); Izgelov et al. (2020b); Izgelov et al. (2020c) | Blackard and Tennes, (1984); Izgelov et al. (2020b) | ||||||||
| Dogs | Mice | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Measured Compounds | CBD, THC, 11-OH-THC | THC, 11-OH-THC, THC-COOH, CBD, CBDV, THCV, CBG | ||||||||
| Matrices | Plasma | Urine | Plasma | Maternal plasma, whole fetus body and amniotic fluid | ||||||
| Mode of administration | Oral | Trasndermal | Sublingual | Intravenous | Intravenous | Intraperitoneal | Oral | Intravenous | Subcutaneous | |
| Cmax (ng/ml) | 346.3–845.5 (CBD) 3.6–77.1 (THC) | 74.3–277.6 (THC) | 18.5–24.5 (THC) 10.5–15.2 (CBD) 1.2–2.2 (11-OH-THC) | 6,950–13,550 (CBD) | 12 µg (CBD) | 22.3–13,575 (THC) 2.0–39.3 (11-OH-THC) 8.3–506.3 (THC-COOH) 14,300 (CBD) 4,000 (CBDV) 880 (THCV) 40,800 (CBG) | 129.5–2,200 (CBD) 470 (CBDV) 240 (THCV) 670 (CBG) | 2,343.3 (CBD) | 1.2–1.6 (THC) 22–34 (CBD) 2 (CBG) | Maternal plasma: 2,615.3 (CBD) Whole fetus body: 598.7 ng/g (CBD) Amniotic fluid: 74.4 (CBD) |
| Tmax (hours) | 2–6 (CBD) 0.5–8 (THC) | 10–12 (THC) | 1–2 (THC, CBD, 11-OH-THC) | 0–0.5 (THC) 0.25–1 (11-OH-THC) 0.5–1 (THC-COOH) 2 (CBD, CBG) 0.5 (CBDV, THCV) | 1–2 (CBD) 0.5 (CBDV, THCV, CBG) | Amniotic fluid: 0.5 (CBD) | ||||
| Half-life (hours) | 1.6–3.3 (CBD) 0.8–3.5 (THC) | 6.8–9.3 (CBD) | 1.8 (CBD) | 0.7–1.8 (THC) 1.2–3.5 (11-OH-THC) 2.7–4.2 (THC-COOH) 4.7 (CBD) 2.9 (CBG), 4.7(CBDV) 5.8 (THCV) | 3.9 (CBD) | Maternal plasma: 4.9 Whole fetus bodies: 2.3 Amniotic fluid: 51.5 | ||||
| Time of sampling | 0–96 h after administration | 0–14 days after the administration | ||||||||
| Articles | Samara et al. (1988); Samara et al. (1990); Hasiwa et al. (2011); Bartner et al. (2018); Fernandez-Trapero et al. (2020) | Bornheim et al. (1995); Deiana et al. (2012); Elmes et al. (2019); Xu et al. (2019); Torrens et al. (2020); Uziel et al. (2020); Ochiai et al. (2021) | ||||||||
| Monkeys | Pigs | Rabbits | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Measured Compounds | THC, 11-OH-THC, THC-COOH | THC | THC | ||||||||
| Matrices | Plasma | Maternal and fetal plasma | Plasma | Plasma | |||||||
| Mode of administration | Intravenous | Oral | Intramuscular | Intravenous | Oral | Intravenous | Intranasal | Ophtalmic | Oral | Sublingual | |
| Cmax (ng/ml) | 5,000 (THC) | 42–239 (THC) 3.9–44.7 (11-OH-THC) 3–53.5 (THC-COOH) | 225–255 (THC) | Maternal: 1,419 (THC), 44 (THC-COOH) Fetal: 83 (THC) THC-COOH not detected | 39.5–161 (THC) | 0.17 (THC) | 3–1,475 (THC) | 20–31 (THC) | 0.3–2.3 (THC) | 0.9 (THC) | 0.5–3.0 (THC) |
| Tmax (hours) | 0.33 (THC) 1–2 (11-OH-THC, THC-COOH) | 0.5–2.3 (THC) | 12 (THC) | 0.33–0.75 (THC) | 0.3–7.5 (THC) | 0.5 (THC) | 3–4 (THC) | ||||
| Half-life (hours) | 2–2.7 (THC) | 7.4–13.6 (THC) | 1.1–66.2 (THC) | ||||||||
| Time of sampling | 0–96 h after administration | 0–48 h after administration | 0–10 days after administration | ||||||||
| Articles | Perlin et al. (1985); Ginsburg et al. (2014); Ochiai et al. (2021) | Brunet et al. (2006); Itin et al. (2020) | Chiang et al. (1983); Leuschner et al. (1986); Mannila et al. (2004); Mannila et al. (2006); Al-Ghananeem et al. (2011) | ||||||||
| Sheeps | Buffalos | Squirrel monkeys | ||
|---|---|---|---|---|
| Measured Compounds | THC | THC-COOH | THC | |
| Matrices | Maternal and fetal plasma | Breast milk | Maternal and child urine | Maternal breast milk, urine and feces and child urine and feces |
| Mode of administration | ||||
| Cmax (ng/ml) | 51 (THC-COOH) | Maternal urine: 17–289 (THC-COOH) Child urine: 8–25 (THC-COOH) | Breast milk: 0.2% of the maternal dose Maternal urine: 42% Maternal feces: 1% Child urine: 0.01% Child feces: 0.12% | |
| Tmax (hours) | Maternal: 10 min Fetal: 90 min | |||
| Half-life (hours) | Maternal and fetal: >10 | |||
| Time of sampling | 0–24 h after administration | 18 h after administration | ||
| Articles | Abrams et al.(1985) | Ahmad and Ahmad,(1990) | Chao et al.(1976) | |