Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Animals and Dosing
2.3. Sample Preparation
2.4. Sample Analysis
2.5. Data Analysis
3. Results
3.1. Formulation Analysis
3.2. Single-Dose Pharmacokinetic Study
3.3. Multiple-Dose Pharmacokinetic Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Kratom Product Alone (n = 4) [35] | Kratom Product Plus Cannabidiol (n = 5) | Fold Change (90% CI Ratio) |
---|---|---|---|
Cmax (ng/mL) | 111.9 ± 15.6 | 253.4 ± 68.3 | 2.3 (1.6, 2.7) |
Tmax (h) | 3.1 ± 1.7 | 17.0 ± 4.6 | 5.4 (24.3, 4.2) |
AUC0–24 (h·ng/mL) | 1306.8 ± 126.1 | 5354.9 ± 1145.5 | 2.8 (1.6, 3.7) |
Parameter | Cannabidiol Product Alone (n = 4) | Cannabidiol Plus Kratom Product (n = 5) | Fold Change (90% CI Ratio) |
---|---|---|---|
Cmax (ng/mL) | 588.8 ± 38.3 | 490.9 ± 69.2 | 0.8 (0.7, 0.9) |
Tmax (h) | 3.8 ± 1.5 | 6.3 ± 1.0 | 1.7 (3.8, 1.3) |
AUC0–24 (h·ng/mL) | 4400.6 ± 319.2 | 4182.6 ± 614.5 | 1.0 (0.8, 1.1) |
Kratom Product Alone (n = 4) [35] | Kratom Product Plus Cannabidiol (n = 5) | |
---|---|---|
Corynantheidine (0.2 mg/kg) | ||
Cmax (ng/mL) | 3.1 ± 0.5 | 12.9 ± 2.0 |
Tmax (h) | 3.1 ± 1.7 | 12.6 ± 11.4 |
AUC0–24 (h·ng/mL) | 30.4 ± 9.1 | 195.9 ± 111.1 |
Speciociliatine (2.2 mg/kg) | ||
Cmax (ng/mL) | 23.8 ± 1.4 | 68.1 ± 5.9 |
Tmax (h) | 3.2 ± 1.6 | 17.0 ± 5.9 |
AUC0–24 (h·ng/mL) | 222.7 ± 22.2 | 989.7 ± 93.7 |
Paynantheine (1.8 mg/kg) | ||
Cmax (ng/mL) | 3.0 ± 1.7 | 19.8 ± 5.8 |
Tmax (h) | 0.08 ± 0.0 | 16.2 ± 4.9 |
AUC0–24 (h·ng/mL) | - | 290.0 ± 96.4 |
7-hydroxymitragynine (<0.1 mg/kg) | ||
Cmax (ng/mL) | 4.0 ± 0.6 | 17.5 ± 2.3 |
Tmax (h) | 3.1 ± 1.7 | 15.0 ± 5.5 |
AUC0–24 (h·ng/mL) | 41.0 ± 7.6 | 189.2 ± 27.7 |
Parameter | Mitragynine | Cannabidiol |
---|---|---|
Cmin,ss (ng/mL) | 91.1 ± 24.9 | 80.9 ± 23.7 |
Cavg,ss (ng/mL) | 151.1 ± 34.7 | 203.8 ± 51.3 |
Cmax,ss (ng/mL) | 217.5 ± 40.0 | 488.6 ± 96.2 |
Fluctuation (%) | 90.0 ± 11.3 | 219.0 ± 42.7 |
Accumulation Index | 1.4 ± 0.1 | 1.8 ± 0.0 |
AUC0–∞ (h·ng/mL) | 2908.0 ± 735.0 | 3519.3 ± 851.1 |
AUC/τ (h·ng/mL) | 1813.1 ± 416.6 | 2446.0 ± 615.1 |
Parameter | Single-Dose | Multiple-Dose |
---|---|---|
Mitragynine | ||
AUC0–∞/dose (h·ng/mL/mg/kg) | 578.6 ± 187.9 | 605.8 ± 153.1 |
V/F (L/kg) | 25.8 ± 7.5 | 28.7 ± 3.7 |
CL/F (L/h/kg) | 2.3 ± 0.5 | 3.1 ± 0.5 |
Cannabidiol | ||
AUC0–∞/dose (h·ng/mL/mg/kg) | 97.8 ± 18.5 | 140.8 ± 34.0 |
V/F (L/kg) | 164.5 ± 26.3 | 192.3 ± 42.1 |
CL/F (L/h/kg) | 11.5 ± 1.6 | 13.0 ± 2.8 |
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Berthold, E.C.; Kamble, S.H.; Kanumuri, S.R.R.; Kuntz, M.A.; Senetra, A.S.; Chiang, Y.-H.; Mukhopadhyay, S.; McCurdy, C.R.; Sharma, A. Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats. Pharmaceutics 2024, 16, 318. https://doi.org/10.3390/pharmaceutics16030318
Berthold EC, Kamble SH, Kanumuri SRR, Kuntz MA, Senetra AS, Chiang Y-H, Mukhopadhyay S, McCurdy CR, Sharma A. Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats. Pharmaceutics. 2024; 16(3):318. https://doi.org/10.3390/pharmaceutics16030318
Chicago/Turabian StyleBerthold, Erin C., Shyam H. Kamble, Siva Rama Raju Kanumuri, Michelle A. Kuntz, Alexandria S. Senetra, Yi-Hua Chiang, Sushobhan Mukhopadhyay, Christopher R. McCurdy, and Abhisheak Sharma. 2024. "Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats" Pharmaceutics 16, no. 3: 318. https://doi.org/10.3390/pharmaceutics16030318
APA StyleBerthold, E. C., Kamble, S. H., Kanumuri, S. R. R., Kuntz, M. A., Senetra, A. S., Chiang, Y.-H., Mukhopadhyay, S., McCurdy, C. R., & Sharma, A. (2024). Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats. Pharmaceutics, 16(3), 318. https://doi.org/10.3390/pharmaceutics16030318