Medicinal Cannabis Does Not Influence the Clinical Pharmacokinetics of Irinotecan and Docetaxel

Engels, Frederike K.; Jong, Floris A. de; Sparreboom, Alex; Mathôt, Ron A. A.; Loos, Walter J.; Kitzen, Jos; Bruijn, Peter de; Verweij, Jaap; Mathijssen, Ron H.J.

doi:10.1634/theoncologist.12-3-291

Cited by 65 publications

(39 citation statements)

References 50 publications

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“…Two studies in Table 3 did not meet inclusion criteria, but are included as they may provide additional insight into the specific pharmacokinetic effects described above. (Chetty et al, 1994;Engels et al, 2007) In a population pharmacokinetic analysis, self-reported regular cannabis use was associated with a 50% increase in estimated chlorpromazine clearance. (Chetty et al, 1994) This may reflect net CYP1A2 induction by non-THC components of smoked marijuana, consistent with results seen with theophylline.…”

Section: Data Not Meeting Inclusion Criteriamentioning

confidence: 99%

Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Stout¹,

Cimino²

2013

Drug Metabolism Reviews

295

230

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Exogenous cannabinoids are structurally and pharmacologically diverse compounds that are widely used. The purpose of this systematic review is to summarize the data characterizing the potential for these compounds to act as substrates, inhibitors, or inducers of human drug metabolizing enzymes, with the aim of clarifying the significance of these properties in clinical care and drug interactions. In vitro data were identified that characterize cytochrome P-450 (CYP-450) enzymes as potential significant contributors to the primary metabolism of several exogenous cannabinoids: tetrahydrocannabinol (THC; CYPs 2C9, 3A4); cannabidiol (CBD; CYPs 2C19, 3A4); cannabinol (CBN; CYPs 2C9, 3A4); JWH-018 (CYPs 1A2, 2C9); and AM2201 (CYPs 1A2, 2C9). CYP-450 enzymes may also contribute to the secondary metabolism of THC, and UDP-glucuronosyltransferases have been identified as capable of catalyzing both primary (CBD, CBN) and secondary (THC, JWH-018, JWH-073) cannabinoid metabolism. Clinical pharmacogenetic data further support CYP2C9 as a significant contributor to THC metabolism, and a pharmacokinetic interaction study using ketoconazole with oromucosal cannabis extract further supports CYP3A4 as a significant metabolic pathway for THC and CBD. However, the absence of interaction between CBD from oromucosal cannabis extract with omeprazole suggests a less significant role of CYP2C19 in CBD metabolism. Studies of THC, CBD, and CBN inhibition and induction of major human CYP-450 isoforms generally reflect a low risk of clinically significant drug interactions with most use, but specific human data are lacking. Smoked cannabis herb (marijuana) likely induces CYP1A2 mediated theophylline metabolism, although the role of cannabinoids specifically in eliciting this effect is questionable.

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Section: Data Not Meeting Inclusion Criteriamentioning

confidence: 99%

Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review

Stout¹,

Cimino²

2013

Drug Metabolism Reviews

295

230

View full text Add to dashboard Cite

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“…However, smoked cannabis decreased the 8‐h area under the plasma concentration–time curve (AUC) of both nelfinavir (−17.4%, P = 0.46) and indinavir (−14.5%, P = 0.07). In a study involving 24 patients with cancer, cannabis administered as a medicinal tea did not alter the pharmacokinetics of the chemotherapy agents irinotecan and docetaxel 18 …”

mentioning

confidence: 96%

“…In a study involving 24 patients with cancer, cannabis administered as a medicinal tea did not alter the pharmacokinetics of the chemotherapy agents irinotecan and docetaxel. 18 articles Inhalation of vaporized cannabis delivers levels of THC and other cannabinoids similar to those from smoked marijuana but without exposure to combustion products. 19 Here we describe the disposition kinetics of sustained-release morphine and oxycodone, as well as pain ratings and other subjective responses, before and after 4 days of treatment with vaporized cannabis.…”

mentioning

confidence: 99%

Cannabinoid–Opioid Interaction in Chronic Pain

Abrams

Couey

Shade

et al. 2011

Clin Pharmacol Ther

281

232

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Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustained-release morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2-4, and in the morning of day 5. Blood sampling was performed at 12-h intervals on days 1 and 5. The extent of chronic pain was also assessed daily. Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration-time curves for either morphine or oxycodone after exposure to cannabis. Pain was significantly decreased (average 27%, 95% confidence interval (CI) 9, 46) after the addition of vaporized cannabis. We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels. The combination may allow for opioid treatment at lower doses with fewer side effects.

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“…Besides regular drugs for the management of nausea and vomiting, cannabis was demonstrated to be effective and was approved by the FDA [58]. No effects on docetaxel PK were demonstrated [59].…”

Section: Interactions With Supportive Medicationmentioning

confidence: 99%