Article Figures & Data
Figures
- Fig. 1.
CBD concentration-time profiles in maternal blood and fetus in pregnant mice. CBD (10 mg/kg) was administered to pregnant mice via the tail vein, and blood was collected via the central vein at various times (0.25, 0.5, 1, 2, 4, 8, and 12 hours). Blood was collected from the central vein. Fetuses were extracted simultaneously. After separation from blood, plasma was analyzed using LC-MS. (A) Maternal plasma (n = 5); (B) fetus (n = 15). The results of the analysis are displayed as mean ± S.D. values of the mean levels with respect to individual pregnant mice at each time point (0.25, 0.5, 1, 2, 4, 8, and 12 hours).
- Fig. 2.
CBD concentration-time profiles in fetal tissue. CBD (10 mg/kg) was administered to pregnant mice via the tail vein, and fetal tissues were dissected at various times (0.25, 0.5, 1, 2, 4, 8, and 12 hours). The homogenate solutions of the organs were analyzed via LC-MS. (A) Fetal brain (n = 15); (B) fetal liver (n = 15); (C) fetal GI tract (n = 15). The results of the analysis are displayed as mean ± S.D. values of the mean levels with respect to individual pregnant mice at each time point (0.25, 0.5, 1, 2, 4, 8, and 12 hours). N.D., not detected.
- Fig. 3.
Estimation of the CBD transfer ratio from mothers to fetuses. A time-course plot of the ratio of the fetus CBD concentration to the maternal plasma CBD concentration was created [maternal plasma (n = 5), fetus (n = 15)]. The results of the analysis are displayed as mean ± S.D. values of the mean levels with respect to individual pregnant mice at each time point (0.25, 0.5, 1, 2, 4, 8, and 12 hours) Concentration ratio = (CBD concentration of fetus (Fig.1B)) / (Maternal plasma CBD concentration (Fig.1A))
- Fig. 4.
Estimation of the CBD transfer ratio from maternal blood to fetal tissue. A time-course plot of the ratio of the fetal tissue CBD concentration to maternal plasma CBD concentration was created [(A) fetal brain/maternal plasma; (B) fetal liver/maternal plasma; (C) fetal GI tract/maternal plasma (n = 15)]. Values are displayed as means ± S.D. N.D., not detected. Concentration ratio = (CBD concentration of each fetal organs (Fig.2A, B, C)) / (Maternal plasma CBD concentration (Fig.1A))
- Fig. 5.
CBD concentration-time profiles of amniotic fluid in pregnant mice. CBD (10 mg/kg) was administered by tail vein injection, and its levels in amniotic fluid were measured at various times via LC-MS [amniotic fluid (n = 5)]. The results of the analysis are displayed as mean ± S.D. values of the mean levels with respect to individual pregnant mice at each time point (0.25, 0.5, 1, 2, 4, 8, and 12 hours).
Tables
- TABLE 1
Pharmacokinetic parameters of cannabidiol in the maternal plasma and fetus
The results of the analysis are displayed as means ± S.D.
AUC0–12 AUCinf MRT0–12 MRTinf t1/2α t1/2β CLtot Vdα Vdβ Maternal: ng*h/ml
Fetal: ng*h/gh l/h per kilogram l/kg Maternal sample (plasma) (n = 5) 1295.2 ± 166.0 1692.1 ± 417.5 1.1 ± 0.07 1.7 ± 0.3 0.7 ± 0.1 4.9 ± 1.2 7.7 ± 1.0 2.2 ± 0.1 55.1 ± 2.4 Fetal sample (whole body) (n = 15) 866.4 ± 214.2 874.5 ± 210.0 1.7 ± 0.2 1.8 ± 0.4 0.8 ± 0.2 2.3 ± 0.5 —a —a —a ↵a Can't calculate.
- TABLE 2
Pharmacokinetic parameters of cannabidiol in the fetal brain, liver, and GI tract
The results of the analysis are displayed as means ± S.D. Numerical data are expressed as means ± S.D. The significance of differences was evaluated using ANOVA, followed by Tukey’s test (AUC0–12, MRT0–12, t1/2α). The Student’s t test was used for the significant difference in t1/2β between brain and liver.
Fetal Sample AUC0–12 AUCinf MRT0–12 MRTinf t1/2α t1/2β ng*h/g tissue h Brain (n = 15) 1078.4 ± 72.3 1224.3 ± 138.9 2.2 ± 0.3 4.7 ± 1.4 0.8 ± 0.1 7.2 ± 2.4 Liver (n = 15) 1519.2 ± 154.3 1572.3 ± 164.7 1.6 ± 0.04 2.2 ± 0.08 0.7 ± 0.1 4.2 ± 0.4 GI tract (n = 15) 668.8 ± 52.1 1150.7 ± 218.6 2.2 ± 0.2 10.5 ± 4.5 1.1 ± 0.1 — a Brain × liver P < 0.0001 —b N.S. —b N.S. P < 0.0001 Brain × GI tract P = 0.0001 —b N.S. —b N.S. Liver × GI tract P < 0.0001 —b N.S. —b N.S. - TABLE 3
Pharmacokinetic parameters of cannabidiol in amniotic fluid
The results of the analysis are displayed as means ± S.D.
In Utero Sample AUC0–12 AUCinf MRT0–12 MRTinf t1/2α t1/2β ng*h/ml h Amniotic fluid (n = 5) 309.9 ± 5.8 1658.6 ± 173.2 6.4 ± 3.8 71.0 ± 8.9 2.0 ± 0.2 51.5 ± 6.4
Data Supplement
- Supplemental Figure -
Figure 1 - Stability of CBD in phosphoric acid aqueous solution.
- Supplemental Figure -
