[{"id":78,"uid":"NPDI-EngCtg","name":"Medicinal Cannabis Does Not Influence the Clinical Pharmacokinetics of Irinotecan and Docetaxel","napdiIdentifier":"PMID: 17405893","overallSummary":"<h4>OBJECTIVE:</h4>\r\n<p>To date, data regarding the potential of cannabinoids to modulate cytochrome P450 isozyme 3A (CYP3A) activity are contradictory. Recently, a standardized medicinal <span class=\"highlight\">cannabis</span> product was introduced in The Netherlands. We anticipated an increased use of medicinal <span class=\"highlight\">cannabis</span> concurrent with anticancer drugs, and undertook a drug-interaction study to evaluate the effect of concomitant medicinal <span class=\"highlight\">cannabis</span> on the pharmacokinetics of irinotecan and docetaxel, both subject to CYP3A-mediated biotransformation.</p>\r\n<h4>PATIENTS AND METHODS:</h4>\r\n<p>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 <span class=\"highlight\">cannabis</span> (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 <span class=\"highlight\">cannabis</span>.</p>\r\n<h4>RESULTS:</h4>\r\n<p>Medicinal <span class=\"highlight\">cannabis</span> 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).</p>\r\n<h4>CONCLUSION:</h4>\r\n<p>Coadministration of medicinal <span class=\"highlight\">cannabis</span>, 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 <span class=\"highlight\">cannabis</span> can be administered concomitantly with both anticancer agents without dose adjustments.</p>","pubmedId":17405893,"embaseId":null,"croIdentifier":"Erasmus MC University Medical Center Rotterdam","croInformation":"Erasmus MC University Medical Center Rotterdam","dateStart":null,"dateEnd":null,"internalComment":null,"status":"published","compoundId":null,"naturalProductUid":"NP-0162af79-839e-40e2-af47-361c659061e9","naturalProductSampleId":null,"studySourceTypeId":1,"naturalProduct":{"uid":"NP-0162af79-839e-40e2-af47-361c659061e9","binomial":"Cannabis sativa","name":"Cannabis","itis":null,"srs":"4495dd37-943e-434d-bf30-ea9172d543c8","source_id":"","conceptId":null},"compound":null,"studySourceType":{"id":1,"name":"Published report"},"experiments":[{"id":307,"uid":"NPDI-4ZUTtw","name":"Irinotecan PK ± medicinal cannabis","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"Table 2","experimentalConditionsComment":null,"resultsComment":"Table 2.","internalComment":null,"objectCompoundId":135,"objectMetaboliteCompoundId":null,"precipitantCompoundId":137,"cytochromeB5Id":null,"studyId":78,"experimentTypeId":9,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":9,"name":"In Vivo Interaction","isInVitro":false,"isTransporter":false,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000071"},"objectCompound":{"id":135,"name":"irinotecan","unii":null,"inChIKey":"UWKQSNNFCGGAFS-XIFFEERXSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":137,"name":"medicinal cannabis","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[{"id":30,"name":"CYP3A","conceptId":null,"experiment_enzyme_xref":{"enzymeId":30,"experimentId":307}}],"transporters":[],"quantifiedMetabolites":[]},{"id":308,"uid":"NPDI-yqEgVA","name":"Docetaxel PK ± medicinal cannabis","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":"Table 3","experimentalConditionsComment":null,"resultsComment":"Table 3.","internalComment":null,"objectCompoundId":136,"objectMetaboliteCompoundId":null,"precipitantCompoundId":137,"cytochromeB5Id":null,"studyId":78,"experimentTypeId":9,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":9,"name":"In Vivo Interaction","isInVitro":false,"isTransporter":false,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000071"},"objectCompound":{"id":136,"name":"docetaxel","unii":null,"inChIKey":"ZDZOTLJHXYCWBA-VCVYQWHSSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":137,"name":"medicinal cannabis","unii":null,"inChIKey":null,"publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[{"id":30,"name":"CYP3A","conceptId":null,"experiment_enzyme_xref":{"enzymeId":30,"experimentId":308}}],"transporters":[],"quantifiedMetabolites":[]}]}]