Cannabis (Cannabis sativa)
Medicinal Cannabis Does Not Influence the Clinical Pharmacokinetics of Irinotecan and Docetaxel
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OBJECTIVE:
To date, data regarding the potential of cannabinoids to modulate cytochrome P450 isozyme 3A (CYP3A) activity are contradictory. Recently, a standardized medicinal cannabis product was introduced in The Netherlands. We anticipated an increased use of medicinal cannabis concurrent with anticancer drugs, and undertook a drug-interaction study to evaluate the effect of concomitant medicinal cannabis on the pharmacokinetics of irinotecan and docetaxel, both subject to CYP3A-mediated biotransformation.
PATIENTS AND METHODS:
Twenty-four cancer patients were treated with i.v. irinotecan (600 mg, n = 12) or docetaxel (180 mg, n = 12), followed 3 weeks later by the same drugs concomitant with medicinal cannabis (200 ml herbal tea, 1 g/l) for 15 consecutive days, starting 12 days before the second treatment. Blood samples were obtained up to 55 hours after dosing and analyzed for irinotecan and its metabolites (SN-38, SN-38G), respectively, or docetaxel. Pharmacokinetic analyses were performed during both treatments. Results are reported as the mean ratio (95% confidence interval [CI]) of the observed pharmacokinetic parameters with and without concomitant medicinal cannabis.
RESULTS:
Medicinal cannabis administration did not significantly influence exposure to and clearance of irinotecan (1.04; CI, 0.96-1.11 and 0.97; CI, 0.90-1.05, respectively) or docetaxel (1.11; CI, 0.94-1.28 and 0.95; CI, 0.82-1.08, respectively).
CONCLUSION:
Coadministration of medicinal cannabis, as herbal tea, in cancer patients treated with irinotecan or docetaxel does not significantly influence the plasma pharmacokinetics of these drugs. The evaluated variety of medicinal cannabis can be administered concomitantly with both anticancer agents without dose adjustments.
1 . Docetaxel PK ± medicinal cannabis (id=NPDI-yqEgVA)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
- CYP3A
Table 3
Results
Table 3.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Parallel
Females
Males
Patients
No marijuana use
12
M = 7, F = 5
Age 58 (27-66)
All with metastatic cancer "for which irinotecan or docetaxel was considered an adequate option, which was refractory to conventional treatment or for which there was no standard regimen."
Please refer to Table 1 in the text for further information
Immediately prior infusion, 30 min after start, just before end of infusion; at 10, 20, 30 min, 1, 1.5, 2, 4, 5, 6, 7.5, 23, 31.5, and 47 hr after EOI
Drug or Natural Product Administration
Intravenous
Injection (250 mL NSS)
180 mg for first treatment, 135 mg or as per previous response for second treatment
Q3W
1-hr infusion, 3 weeks
Oral
Solution
18% THC, 0.8% CBD (200 mL, 1 g/L)
QPM
15 days starting day 10 of first treatment
Office for Medicinal Cannabis, The Hague, The Netherlands
Herbal tea
Not specified
2 . Irinotecan PK ± medicinal cannabis (id=NPDI-4ZUTtw)
In Vivo Interaction Study
No Effect (based on bioequivalence limits) was detected.
- CYP3A
Table 2
Results
Table 2.
| Sample | Compound measured | Value | Measurement | Study sequence | Additional information | N replicates |
|---|
Experimental Conditions
Parallel
Females
Males
Patients
No marijuana use
12
M = 7, F = 5
Age 58 (27-66)
All with metastatic cancer "for which irinotecan or docetaxel was considered an adequate option, which was refractory to conventional treatment or for which there was no standard regimen."
Please refer to Table 1 in the text for further information
Immediate prior infusion, 30 min before end of infusion (EOI); at 10, 20, 30 min, 1, 1.5, 2, 3, 4, 5, 6, 22.5, 30, 46.5, and 54 hr after EOI
Drug or Natural Product Administration
Intravenous
Injection (250 mL NSS)
600 mg for first treatment, 450 mg or as per previous response
QW
90-min infusion, 1 week
Oral
Solution
18% THC, 0.8% CBD (200 mL, 1 g/L)
QPM
15 days starting day 10 of first treatment
Office for Medicinal Cannabis, The Hague, The Netherlands
Herbal tea
Not specified
Pharmacodynamics (PD) & Adverse Events
Hepatobiliary disorders
35900000
Immune system disorders
36000000
Varying degrees of reduction of WBC and neutrophil count. Please refer to Table 4 for further information.
Hepatobiliary disorders
35900000
Immune system disorders
36000000
Varying degrees of reduction of WBC and neutrophil count. Please refer to Table 4 for further information.