Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma

Troels K Bergmann, Anne M Filppula, Terhi Launiainen, Flemming Nielsen, Janne Backman, Kim Brosen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

AIM: The aim of this case report is to describe a novel pharmacokinetic drug-drug interaction between the antiplatelet agent clopidogrel and the antineoplastic agent paclitaxel.

METHODS: The patient was identified in a previously described cohort of 93 patients with ovarian carcinoma treated with paclitaxel. The effect of clopidogrel acyl-β-D-glucuronide on the metabolism of paclitaxel was assessed in human liver microsomes. The analysis of clopidogrel in plasma and the quantification of paclitaxel and 6α-hydroxypaclitaxel in in vitro samples were performed by liquid chromatography tandem mass spectrometry.

RESULTS: The patient was a 60 year old female treated with an unknown dose of clopidogrel at the time of paclitaxel therapy. Clopidogrel was present in all the three plasma samples obtained during paclitaxel dosing. Estimated unbound paclitaxel clearance was 238 L/h, which is only 62% of the cohort geometric mean (385 L/h; range 176-726). She was hospitalised thrice, developed severe neuropathy and paclitaxel treatment was subsequently discontinued. In vitro, 30 min preincubation with 100 μM clopidogrel acyl-β-D-glucuronide inhibited the depletion rate of 0.5 μM paclitaxel by 51% and the formation rate of 6α-hydroxypaclitaxel by 77%.

CONCLUSION: This is the first report of a clopidogrel-paclitaxel interaction, suggesting that clinically used doses of clopidogrel can reduce the CYP2C8-mediated systemic clearance of paclitaxel, leading to an increased risk of paclitaxel toxicity. Caution should be exercised whenever the simultaneous use of paclitaxel and clopidogrel cannot be avoided. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftBritish Journal of Clinical Pharmacology
Vol/bind81
Udgave nummer2
Sider (fra-til)313-315
ISSN0306-5251
DOI
StatusUdgivet - 7. okt. 2015

    Fingerprint

Citationsformater