Docetaxel pharmacokinetics

P-gp is responsible for transport of the carboxylate form of irinotecan (64). The homozygous mutant 8 polymorphism has been associated with significantly increased exposure to irinotecan and its active metabolite SN-38 (65). Furthermore, significantly decreased docetaxel clearance was found in patients homozygous mutant for P-gp 8 (66), although Goh et al. (67) did not find a significant effect of this polymorphism on docetaxel pharmacokinetics. Also, a trend to an increased AUC of tipifamib in patients with the homozygous mutant allele compared to patients with only one or no mutant alleles of 8 was found in a study by Sparreboom et al. (68). In a study by Kishi et al. (40), the mutant allele for 6 was also correlated with a lower clearance of etoposide in children with ALL. 

Marchettini,P., Stuart, A.,Mohamed,F.,Yoo,D., and Sugarbaker, P. H. (2002),Docetaxel Pharmacokinetics and tissue levels after intraperitoneal and intravenous administration in a rat model, Cancer Chemother. Pharmacol., 49,499-503. 

Docetaxel pharmacokinetics are similar to those of paclitaxel. Its elimination tj is -12 hours, and its clearance is 22 L/hour/nP. Clearance is primarily through CYP3A4- and CYP3A5-medi-ated hydroxylation, leading to inactive metabolites. Unlike paclitaxel, the pharmacokinetics or docetaxel are linear up to doses of 115 mg/nP. 

The AUCs of ifosfamide and its metabolites were lower when ifosfamide was given immediately after docetaxel than when it was given 24 hours before docetaxel, due to increased clearance. Docetaxel pharmacokinetics were unaltered by ifosfamide. This supports the evidence that the maximum tolerated dose is greater when ifosfamide is given after docetaxel. The mechanism is unknown, but it has been suggested that docetaxel may competitively inhibit the activation of ifosfamide by the cytochrome P450 isoenzyme CYP3A4. These results showthat the toxicity, and possibly efficacy, of the combination are schedule dependent. More study is needed. Cyclophosphamide does not appear to alter doeetaxel pharmacokinetics. For full details see also Taxanes + Cyclophosphamide , p.661. 

One study found that giving paclitaxel before gemeitabine increased the gemeitabine levels by 2S%, but other studies did not find a pharmacokinetic interaction. Gemeitabine distribution may be altered by docetaxel, but docetaxel pharmacokinetics are not affected. The clinical response to the combination of gemcit-... 

In a study of gemeitabine and docetaxel, given on days 1 and 8 of a 21 -day cycle, drug toxicity and pharmacokinetics were unaffected by the relative order of their administration. However, in another study, it appeared that while docetaxel pharmacokinetics were unaffected, the distribution of gemeitabine was altered by docetaxel, although there was no clear relationship between this and toxicity. ... 

In contrast to paclitaxel, early studies did not reveal any obvious sequence dependent toxicity for the combination of docetaxel and cisplatin. In addition, cisplatin did not cause any significant changes in docetaxel pharmacokinetics. ... 

There is some evidence to suggest that the toxicity associated with combinations of paclitaxel and cyclophosphamide is dependent on the order of administration. Results from one study indicate that docetaxel pharmacokinetics are unaltered by cyclophosphamide. 

In breast cancer patients undergoing treatment with docetaxel (30 mg/m /week), coadministration with 1200 mg garlic daily did not significantly affect docetaxel pharmacokinetics (Cox et al. 2006). 

Docetaxel, another taxane, binds to tubulin to promote microtubule assembly. The pharmacokinetics of docetaxel are best described by a three-compartment model, with an a half-life of 0.08 hours, a 3 half-life of 1.6 to 1.8 hours, and a terminal half-life of 65 to 73 hours.14 Docetaxel has activity in the treatment of breast, non-small cell lung, prostate, bladder, esophageal, stomach, ovary, and head and neck cancers. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid... 

Malingre, M.M., et al. 2001. Pharmacokinetics of oral cyclosporin A when co-administered to enhance the absorption of orally administered docetaxel. Eur J Clin Pharmacol 57 305. 

Bruno, R. Vivier, N. Veyrat-Follet, C. Monaty, G. Rhodes, G.R. Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationship for docetaxel. Invest. New Drugs 2001, 19 (2), 163-169. 

Rosing H, Lustig V, van Warmerdam LJ, Hiiizmg MT, ten Bokkel Huinink WW, ScheUens JH, Rodenhuis S, Bult A, Beijnen JH. Pharmacokinetics and metabolism of docetaxel administered as a 1-h intravenous infusion. Cancer Chemother Pharmacol 2000 45(3) 213-18. 

Zamboni WC, Egorin MJ, Van Echo DA, Day RS, Meisenberg BR, Brooks SE, Doyle LA, Nemieboka NN, Dobson JM, Tait NS, Tkaczuk KH. Pharmacokinetic and pharmacodynamic study of the combiuatiou of docetaxel aud topotecan in patients with sohd tumors. J Chn Oncol 2000 18(18) 3288-94. 

Franke RM, Carducci MA, Rudek MA, Baker SD, Sparreboom A (2010) Castration-dependent pharmacokinetics of docetaxel in patients with prostate cancer. J Clin Oncol 28 4562 567... 

Hudachek SF, Gustafson DL (2013) Incorporation of ABCB1-mediated transport into a physiologically-based pharmacokinetic model of docetaxel in mice. J Pharmacokinet Pharmacodyn 40(4) 437-449... 

Bruno, R., Vivier, N., Vergniol, J.C., De Phillips, S.L., Mon-tay, G., and Shiener, L.B. A population pharmacokinetic model for docetaxel (Taxotere) Model building and validation. Journal of Pharmacokinetics and Biopharmaceutics 1996 24 153-172. 

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. 

For centuries, plants have been a unique source of therapeutically significant alkaloids and they continue to be excellent sources of drugs. Furthermore, alkaloids of natural origin serve as a model for the semisynthesis or the synthesis of derivatives which have improved pharmacokinetic properties, a higher efficacy and/or less toxicity. One of the most recent examples is the isolation of the anticancer agent, called taxol, from the stem bark Of the Pacific yew tree Taxus brevifolia in 1971 by Wani and co-workers [1] and the development, a few years later, of docetaxel, a semisynthetic derivative obtained from 10-deacetyl-baccatin III [2]. 

Tolcher A W, Chi K, et al. (2005). A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 11 3854-3861. 

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