Coadministration of Cyclosporine Strongly Enhances the Oral Bioavailability of Docetaxel

Malingré, Mirte M.; Richel, Dick J.; Beijnen, Jos H.; Rosing, Hilde; Koopman, Franciska J.; Huinink, W.W. ten Bokkel; Schot, Margaret; Schellens, Jan H.M.

doi:10.1200/jco.2001.19.4.1160

Cited by 191 publications

(107 citation statements)

References 16 publications

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“…2B) [157]. Cyclosporin A also effectively resulted in a greater oral bioavailability of docetaxel, 91% versus 8% [158]. Elacridar, an effective inhibitor of BCRP as well as of P-gp produced a greater oral bioavailability of topotecan, 97% versus 40% [159].…”

Section: Possible Clinical Benefit Of Drug-drug Interactionsmentioning

confidence: 99%

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

et al. 2007

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Key Words. P-glycoprotein • Drug interaction • Complementary and alternative medicine • CAM • Pharmacokinetics Pharmacodynamics LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify important sources of variability in drug exposure caused by drug interactions mediated by P-glycoprotein.2. Describe how unwanted drug-drug interactions may lead to unexpected serious toxicity or undertreatment.3. Prevent these interactions by individualizing pharmacotherapy; this means selecting noninteracting drugs or adapting the dose of (the) interacting drug(s).Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThe importance of P-glycoprotein (P-gp) in drug-drug interactions is increasingly being identified. P-gp has been reported to affect the pharmacokinetics of numerous structurally and pharmacologically diverse substrate drugs. Furthermore, genetic variability in the multidrug resistance 1 gene influences absorption and tissue distribution of drugs transported. Inhibition or induction of P-gp by coadministered drugs or food as well as herbal constituents may result in pharmacokinetic interactions leading to unexpected toxicities or undertreatment. On the other hand, modulation of P-gp expression and/or activity may be a useful strategy to improve the pharmacological profile of anticancer P-gp substrate drugs. In recent years, the use of complementary and alternative medicine (CAM), like herbs, food, and vitamins, by cancer patients has increased significantly. CAM use substantially increases the risk for interactions with anticancer drugs, especially because of the narrow therapeutic window of these compounds. However, for most CAMs, it is unknown whether they affect metabolizing enzymes and/or drug transporter activity. Clinically relevant interactions are reported between St John's wort or grapefruit juice and anticancer as well as nonanticancer drugs. CAM-drug interactions could explain, at least in part, the large interindividual variation in efficacy and toxicity associated with drug therapy in both cancer and noncancer patients.

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Section: Possible Clinical Benefit Of Drug-drug Interactionsmentioning

confidence: 99%

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

et al. 2007

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“…This increase in systemic exposure can be explained by inhibition of CYP3A4, as well as by P-gp inhibition in the gastrointestinal tract by CsA, but the magnitude of both mechanisms cannot be determined exactly. The effect of CsA on the bioavailability of docetaxel was less pronounced in mice [111] compared with humans [137], but the reasons for this modest effect in mice are not clear. A phase II study in advanced breast cancer with weekly oral docetaxel plus CsA was also performed at our institute.…”

Section: Improvement Of Oral Drug Treatment By Transporter Inhibitionmentioning

confidence: 99%

Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview

2002

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The oral bioavailability of many cytotoxic drugs is low and/or highly variable. This can be caused by high affinity for drug transporters and activity of metabolic enzymes in the gastrointestinal tract and liver. In this review, we will describe the main involved drug transporters and metabolic enzymes and discuss novel methods to improve oral treatment of affected substrate drugs. Results of preclinical and clinical phase I and II studies will be discussed in which affected substrate drugs, such as paclitaxel, docetaxel, and topotecan, are given orally in combination with an inhibitor of drug transport or drug metabolism. Future randomized studies will, hopefully, confirm that this strategy for oral treatment is at least as equally effective and safe as standard intravenous administration of these drugs. The Oncologist 2002;7:516-530

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“…13 It is generally believed that P-glycoprotein (Pgp)-mediated efflux in the intestine and cytochrome P450 (CYP)3A-mediated first-pass metabolism in the intestine and/or liver, together with poor aqueous solubility (0.025 µg/mL), are primarily responsible for the low oral bioavailability of docetaxel. 14,15 Several studies have shown that the oral bioavailability of docetaxel can be enhanced significantly by coadministration of Pgp and/or CYP3A inhibitors, such as cyclosporin A, ritonavir, interferon-alpha, and ontogen (ONT-093). 14,[16][17][18] However, the usefulness of these drugs in clinical practice is limited, especially for repeated administration, because of the risk of side effects, which include immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

Cho¹,

Park²,

Yoon³

et al. 2014

IJN

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Docetaxel is a potent anticancer drug, but development of an oral formulation has been hindered mainly due to its poor oral bioavailability. In this study, solid lipid nanoparticles (SLNs) surface-modified by Tween 80 or D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) were prepared and evaluated in terms of their feasibility as oral delivery systems for docetaxel. Tween 80-emulsified and TPGS 1000-emulsified tristearin-based lipidic nanoparticles were prepared by a solvent-diffusion method, and their particle size distribution, zeta potential, drug loading, and particle morphology were characterized. An in vitro release study showed a sustained-release profile of docetaxel from the SLNs compared with an intravenous docetaxel formulation (Taxotere®). Tween 80-emulsified SLNs showed enhanced intestinal absorption, lymphatic uptake, and relative oral bioavailability of docetaxel compared with Taxotere in rats. These results may be attributable to the absorption-enhancing effects of the tristearin nanoparticle. Moreover, compared with Tween 80-emulsified SLNs, the intestinal absorption and relative oral bioavailability of docetaxel in rats were further improved in TPGS 1000-emulsified SLNs, probably due to better inhibition of drug efflux by TPGS 1000, along with intestinal lymphatic uptake. Taken together, it is worth noting that these surface-modified SLNs may serve as efficient oral delivery systems for docetaxel.

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Coadministration of Cyclosporine Strongly Enhances the Oral Bioavailability of Docetaxel

Cited by 191 publications

References 16 publications

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview

Surface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptake

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