Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel.
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.


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).


CONCLUSIONS
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.
Engels
Frederike K
FK
Department of Medical Oncology, Erasmus MC University Medical Center Rotterdam - Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
de Jong
Floris A
FA
Sparreboom
Alex
A
Mathot
Ron A A
RA
Loos
Walter J
WJ
Kitzen
Jos J E M
JJ
de Bruijn
Peter
P
Verweij
Jaap
J
Mathijssen
Ron H J
RH
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D000077143:Docetaxel; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D043823:Taxoids / Q000493:pharmacokinetics*
D000972:Antineoplastic Agents, Phytogenic; D002186:Cannabinoids; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D051544:Cytochrome P-450 CYP3A; D002166:Camptothecin