High-performance liquid chromatographic procedure for the quantitative determination of paclitaxel (Taxol®) in human plasma

Willey, Tracy A.; Bekos, Evan J.; Gaver, Robert C.; Duncan, Glenn F.; Tay, Lee K.; Beijnen, Jos H.; Farmen, Raymond H.

doi:10.1016/0378-4347(93)80100-i

Cited by 99 publications

(59 citation statements)

References 6 publications

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“…Whole blood was centrifuged immediately after withdrawal during 5 minutes at 3,000 rpm, and the plasma fraction was stored at À20jC until analysis. The plasma concentrations of paclitaxel was determined by a validated isocratic high-performance liquid chromatographic method with solid-phase extraction as the sample pretreatment procedure, as has been described in detail elsewhere (34,35). The quantitation range of the highperformance liquid chromatographic method was 10 to 10,000 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

Quantitative Effect of Gender, Age, Liver Function, and Body Size on the Population Pharmacokinetics of Paclitaxel in Patients with Solid Tumors

Joerger

Huitema

Bongard

et al. 2006

Clinical Cancer Research

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102

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Background:The aim of this study was to quantitatively assess the effect of anthropometric and biochemical variables and third-space effusions on paclitaxel pharmacokinetics in solid tumor patients. Materials and Methods: Plasma concentration-time data of paclitaxel were collected in patients with non^small cell lung cancer (n = 84), ovarian cancer (n = 40), and various solid tumors (n = 44), totaling 168 patients. Paclitaxel was given as a 3-hour infusion (n = 163) at doses ranging from 100 to 250 mg/m 2 , or as a 24-hour infusion (n = 5) at a dose of 135 or 175 mg/m 2 . Data were analyzed using nonlinear mixed-effect modeling. Results: A three-compartment model with saturable elimination and distribution was used to describe concentration-time data. Male gender and body surface area were positively correlated with maximal elimination capacity of paclitaxel (VM EL ); patient age and total bilirubin were negatively correlated withVM EL (P < 0.005 for all correlations).Typically, male patients had a 20% higher VM EL ; a 0.2 m 2 increase of body surface area led to a 9% increase of VM EL ; a 10-year increase of patient age led to a 5% decrease of VM EL ; and a 10-Amol increase of total bilirubin led to a 14% decrease of VM EL . Third-space effusions were not correlated with paclitaxel pharmacokinetics. Conclusions: This extended retrospective population analysis showed patient gender to significantly and independently affect paclitaxel distribution and elimination. Body surface area, total bilirubin, and patient age were confirmed to affect paclitaxel elimination. This pharmacokinetic model allowed quantification of the covariate effects on the elimination of paclitaxel and may be used for covariate-adapted paclitaxel dosing.Paclitaxel formulated in Cremophor EL is regularly administered to patients with non -small cell lung cancer (NSCLC), ovarian cancer, and breast cancer. The pharmacokinetics of paclitaxel were initially believed to be linear, but Sonnichsen and Gianni reported that paclitaxel pharmacokinetics were best described with a two-and three-compartment model, respectively, with saturable elimination and saturable distribution to the tissues (1, 2). Later, the formulation vehicle of paclitaxel, Cremophor EL, was reported to be the cause of the (apparent) nonlinear plasma behavior of paclitaxel, probably by entrapment of paclitaxel into micelles (3 -7). Generally, substantial interpatient variability of paclitaxel pharmacokinetic variables has been noted (8).Hepatic metabolism and biliary excretion are the most important elimination routes of paclitaxel and its metabolites (9). Paclitaxel has been shown to bind extensively to plasma proteins (from 95% to < 97%), with high central (mean = 13.8 L/m 2 ) and steady-state (mean = 182 L/m 2 ) volumes of distribution (10-13). However, data on specific tissue and compartment distribution of paclitaxel in humans following i.v. administration are limited. Paclitaxel concentrations in ascites have been analyzed in single patients, where the concentration ...

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Section: Methodsmentioning

confidence: 99%

Quantitative Effect of Gender, Age, Liver Function, and Body Size on the Population Pharmacokinetics of Paclitaxel in Patients with Solid Tumors

Joerger

Huitema

Bongard

et al. 2006

Clinical Cancer Research

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102

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“…Paclitaxel was determined in plasma using a validated isocratic high-performance liquid chromatographic method with solid phase extraction as sample pretreatment as described previously (14,15). The quantitation range of the method was 10 -10,000 ng/ml.…”

Section: Methodsmentioning

confidence: 99%

Bayesian Pharmacokinetically Guided Dosing of Paclitaxel in Patients with Non-Small Cell Lung Cancer

Jonge

Bongard²,

Huitema³

et al. 2004

Clinical Cancer Research

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Purpose: Paclitaxel is a taxane derivative with a profound antitumor activity against a variety of solid tumors. In a previous clinical study in patients with non-small cell lung cancer (NSCLC) treated with paclitaxel, it was shown that paclitaxel plasma concentrations of 0.1 mol/liter for >15 h were associated with prolonged survival. The purpose of this study was to evaluate the feasibility of Bayesian dose individualization to attain paclitaxel plasma concentrations >0.1 mol/liter for >15 h.Experimental Design: Patients with stage IIIb-IV NSCLC were treated with paclitaxel and carboplatin once every 3 weeks for a maximum of six courses. During the first course, a standard paclitaxel dose of 175 mg/m 2 was administered i.v. in 3 h. In subsequent courses, the paclitaxel dose was individualized based on observed paclitaxel concentrations in plasma during the previous course(s) using a Bayesian algorithm. The paclitaxel dose of a subsequent course was increased to the lowest dose for which the predicted time period during which the paclitaxel plasma concentration exceeds 0.1 mol/liter was >15 h.Results: A total of 25 patients have been included in the study (92 evaluable courses). During the first course, the median time period above the threshold concentration was 16.3 h (range, 7.6 -31.6 h), and was <15 h for 9 patients (36%). During subsequent individualized courses, the time period above the threshold concentration was <15 h in 23% (5 of 22), 14% (2 of 14), 23% (3 of 13), 11% (1 of 9), and 11% (1 of 9) of the patients in the second, third, fourth, fifth, and sixth course, respectively. Dose increments, ranging from 5 to 65 mg/m 2 , were performed in 29 of the 67 individualized courses. Patients with increased individualized doses had similar regimen related toxicities compared with those remaining at a dose of 175 mg/m 2 . Toxicity was reversible and manageable, and was mainly hematological (granulocytopenia CTC grade 3/4 in 80% of the patients). The objective response rate was 20%. Conclusions:The results indicate that the applied pharmacokinetically guided dosing strategy for paclitaxel is safe and technically feasible. A randomized study is necessary to demonstrate whether dose individualization may result in improved activity and efficacy in patients with NSCLC.

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“…To find the quantity of the micelle-incorporated paclitaxel, each paclitaxel-containing micelle preparation was filtered through a 200 nm polycarbonate filter (Millipore Co., Bedford, MA), and the percentage of the paclitaxel in the filtrate (micellized paclitaxel) was determined using the HPLC method as described previously (Willey et al 1993). The value obtained was named the micellization efficiency (calculated from calibration curves).…”

Section: Efficiency Of Paclitaxel Incorporationmentioning

confidence: 99%

Polymeric micelles for delivery of poorly soluble drugs: Preparation and anticancer activityin vitroof paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids

Wang

Mongayt

Torchilin

2005

Journal of Drug Targeting

170

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Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and cationic Lipofectin® lipids (LL) have been prepared. Micelles with the optimized composition (PEG-PE/ST/LL/paclitaxel = 12/12/2/1 by weight) had an average micelle size of about 100 nm, and zeta-potential of about 26 mV. Micelles were stable and did not release paclitaxel when stored at 4°C in the darkness (just 2.9% of paclitaxel have been lost after 4 months with the particle size remaining unchanged). The release of paclitaxel from such micelles at room temperature was also insignificant. However, at 37°C, approx. 16% of paclitaxel was released from PEG-PE/ST/LL/paclitaxel micelles in 72 h, probably, because of phase transition in the ST-containing micelle core. In vitro anticancer effects of PEG-PE/ ST/LL/paclitaxel and control micelles were evaluated using human mammary adenocarcinoma (BT-20) and human ovarian carcinoma (A2780) cell lines. Paclitaxel in PEG-PE/ST/LL micelles demonstrated the maximum anti-cancer activity. Cellular uptake of fluorescently-labeled paclitaxelcontaining micelles by BT-20 cells was investigated using a fluorescence microscopy. It seems that PEG-PE/ST/LL micelles, unlike micelles without the LL component, could escape from endosomes and enter the cytoplasm of BT-20 cancer cells thus increasing the anticancer efficiency of the micellar paclitaxel.

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High-performance liquid chromatographic procedure for the quantitative determination of paclitaxel (Taxol®) in human plasma

Cited by 99 publications

References 6 publications

Quantitative Effect of Gender, Age, Liver Function, and Body Size on the Population Pharmacokinetics of Paclitaxel in Patients with Solid Tumors

Quantitative Effect of Gender, Age, Liver Function, and Body Size on the Population Pharmacokinetics of Paclitaxel in Patients with Solid Tumors

Bayesian Pharmacokinetically Guided Dosing of Paclitaxel in Patients with Non-Small Cell Lung Cancer

Polymeric micelles for delivery of poorly soluble drugs: Preparation and anticancer activityin vitroof paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids

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