Paclitaxel drug interactions

The possible impact of co-administered chemotherapies and radiation therapy on the PK of cetuximab was furthermore assessed using the population PK approach, as described in Section 14.6. The co-administered chemotherapies included cisplatin, carboplatin, paclitaxel, doxorubicin, irinotecan, and gemcitabine. The results of the analysis indicate that neither the co-administered chemotherapies nor radiation therapy had a significant impact on the PK of cetuximab. This finding suggests that the potential for PK-based drug-drug interactions with cetuximab is low. 

Jamis-Dow CA, Pearl ML, Watkins PB, et al. Predicting drug interactions in vivo from experiments in vitro human studies with paclitaxel and ketoconazole. Am J Clin Oncol 1997 20 592-599. 

Drug interactions with paclitaxel have been reviewed (52). The most important of these are the pharmacodynamic interactions with other cytostatic drugs, but pharmacokinetic interactions have also been described. 

Schedules for optimal use alone or in combination with other drugs, including doxorubicin and cisplatin, still are evolving. Drug interactions have been noted the sequence of cisplatin preceding paclitaxel decreases paclitaxel clearance and produces greater toxicity than the opposite schedule. Paclitaxel decreases doxorubicin clearance and enhances cardiotoxicity, whereas docetaxel has no apparent effect on anthracycline pharmacokinetics. 

Bundow D, Aboulafia DM. Potential drug interaction with paclitaxel and highly active antiretroviral therapy in two patients with AIDS-associated Kaposi sarcoma. Am J Clin Oncol (2004) 27, 81-4. 

Fetell MR, Grossman SA, Fisher JD, Erlanger B, Rowinsl E, Stockel J, Piantadosi S. Preirradiation paclitaxel in glioblastoma multiforme efficacy, phaimacolc, and drug interactions. New approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin 0 <7o/(1997) 15, 3121-8. 

Wang Y Wang M, Qi H, Pan P, Hou T, Li J, He G, Zhang H (2014) Pathway-dependent inhibition of paclitaxel hydroxylation by kinase inhibitors and assessment of drug-drug interaction potentials. Drug Metab Dispos 42 782-795... 

In most studies where a supraadditive interaction was seen, cells were incubated with the drug prior to irradiation (38). In general the use of moderate concentrations (5-100 nmol/L) of paclitaxel in the culture medium for over 24 h lead to maximum sensitization. Most studies used actively proliferating cells in order to conduct their experiments and most investigators reached the conclusion that maximal radiosensitization occurred when cells were arrested in G2 and M, as this part of the cell cycle is the most sensitive to radiation damage. This assumption does, however, presuppose that the majority of the G2/M arrested cells will not die unless they are exposed to ionizing XRT. Plateau phase, i.e., nonproliferating, cells were found to be sensitized to radiation... 

The combination of structural simplicity of epothilones with respect to paclitaxel, together with their very interesting activity profile appealed different research teams, interested to overcome limitations of taxanes (poor solubility, multi drug-resistance - MDR [61-63]). Investigations on epothilones were focused on the interaction between the ligands and the paclitaxel binding site (as well as the possible similar portions between epothilones and taxanes) in order to find common pharmacopores to be used in activity improvement and design of novel molecules. 

Natural products have provided some of the most effective drugs for the treatment of cancer, including such well-known drugs as paclitaxel (Taxol Bristol-Myers Squibb) adriamycin, vinblastine, and vincristine. Natural products have also provided many compounds that have led to the discovery of new biochemical mechanisms. This review summarizes the major natural products in clinical use today and introduces several new ones on the cusp of entering clinical practice. The review is organized by mechanism of action, with compounds that interact with proteins discussed first, followed by compounds that interact with RNA or DNA. 

Phospholipid polymers having a 2-methacryloylox-yethyl phosphorylcholine (MPC) were investigated as a solubilizer for paclitaxel. The paclitaxel solubility was observed to increase up to 5.0mg/ml in the presence of a copolymer of MPC and Ai-butyl methacrylate (BMA), poly(MPC-co-BMA), with 70mol% of the BMA unit. The MPC polymer forms a polymer aggregate with the diameter of 23 nm, called a polymeric lipid nanosphere, in aqueous media by hydrophobic interaction, which may solubilize hydrophobic drugs. 

There is some evidence that there is a clinically significant pharmacokinetic interaction of paclitaxel with cisplatin. When cisplatin was given before pachtaxel, the clearance rate of paclitaxel was 25% less than when the two drugs were given in the opposite sequence. In consequence, neutropenia was more profound with the former schedule (281). In addition, in experimental studies, cytotoxicity increased when human ovarian carcinoma cells were... 

Liposomes are predominantly used as carriers for hydrophilic molecules that are encapsulated within the aqueous inner volume which is confined by the lipid bilayer. These molecules generally do not interact with the lipid moiety of the vesicle. Long circulating liposomes modified with poly (ethylene glycol) (PEG) and other formulations carrying encapsulated cytotoxic drugs such as doxoru-bicine, paclitaxel, vincristine, lurtotecan and others are clinically approved chemotherapeutic liposome formulations (1-5). 

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