Population pharmacokinetics of docetaxel during phase I studies using nonlinear mixed-effect modeling and nonparametric maximum-likelihood estimation

Launay-Iliadis, M. C.; Bruno, R.; Cosson, V.; Vergniol, J. C.; Oulid-Aissa, D.; Marty, M.; Clavel, M.; Aapro, M.; Bail, N. Le; Iliadis, Athanassios

doi:10.1007/s002800050366

Cited by 7 publications

(10 citation statements)

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“…Age has been shown to affect many physiological parameters such as height, weight, protein levels, renal function, metabolic capacity and many others. It is well known that clearance tends to decrease with age for many drugs [29,30]. It has been shown that the MPPGL (microsomal protein per gram of liver) typically increases from birth to approximately 28 years (40 mg/g) followed by a gradual decrease with age (mean of 29 mg/g at 65 years) [31].…”

Section: Discussionmentioning

confidence: 99%

A physiologically based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer

Cheeti¹,

Budha²,

Rajan³

et al. 2013

Biopharm & Drug Disp

120

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Potential differences in pharmacokinetics (PK) between healthy subjects and patients with cancer were investigated using a physiologically based pharmacokinetic approach integrating demographic and physiological data from patients with cancer. Demographic data such as age, sex and body weight, and clinical laboratory measurements such as albumin, alpha-1 acid glycoprotein (AAG) and hematocrit were collected in ~2500 patients with cancer. A custom oncology population profile was built using the observed relationships among demographic variables and laboratory measurements in Simcyp® software, a population based ADME simulator. Patients with cancer were older compared with the age distribution in a built-in healthy volunteer profile in Simcyp. Hematocrit and albumin levels were lower and AAG levels were higher in patients with cancer. The custom population profile was used to investigate the disease effect on the pharmacokinetics of two probe substrates, saquinavir and midazolam. Higher saquinavir exposure was predicted in patients relative to healthy subjects, which was explained by the altered drug binding due to elevated AAG levels in patients with cancer. Consistent with historical clinical data, similar midazolam exposure was predicted in patients and healthy subjects, supporting the hypothesis that the CYP3A activity is not altered in patients with cancer. These results suggest that the custom oncology population profile is a promising tool for the prediction of PK in patients with cancer. Further evaluation and extension of this population profile with more compounds and more data will be needed.

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Section: Discussionmentioning

confidence: 99%

A physiologically based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer

Cheeti¹,

Budha²,

Rajan³

et al. 2013

Biopharm & Drug Disp

120

View full text Add to dashboard Cite

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“…Nevertheless, due to its flexibility and robustness in its algorism, this approach has been applied far beyond its original scope. For example, it has also been used to describe rich data from phase I or phase IIa studies 13–17 . To substantiate the population pharmacokinetic modeling results in the current study, traditional individual compartmental modeling was also conducted.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has also been used to describe rich data from phase I or phase IIa studies. [13][14][15][16][17] To substantiate the population pharmacokinetic modeling results in the current study, traditional individual compartmental modeling was also conducted. The individual compartmental modeling yielded results similar to those via the population modeling.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Safety of Golimumab, a Fully Human Anti‐TNF‐α Monoclonal Antibody, in Subjects With Rheumatoid Arthritis

Zhou¹,

Jang²,

Fleischmann

et al. 2007

The Journal of Clinical Pharma

175

101

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Golimumab is a fully human antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned to receive a single infusion of placebo or golimumab (0.1, 0.3, 1, 3, 6, or 10 mg/kg). Serum concentrations of golimumab were determined using a validated enzyme-linked immunosorbent assay method. In addition to the noncompartmental analysis and compartmental modeling, a population pharmacokinetics analysis using NONMEM was also conducted. Both the maximum serum concentration and the area under the serum concentrationtime curve appeared to increase in a dose-proportional manner. The median half-life ranged from 7 to 20 days. A 2-compartment population pharmacokinetic model adequately described the pharmacokinetics of golimumab. The following pharmacokinetic parameters (typical value [% coefficient of variation]) were estimated from the population pharmacokinetic model: clearance (CL: 0.40 [10.1%] L/d), volume of distribution in the central compartment (V(c): 3.07 [6.4%] L), intercompartmental clearance (Q: 0.42 [15.5%] L/d), and volume of distribution in the peripheral compartment (V(p): 3.68 [11.8%] L). Interindividual variability of the pharmacokinetic parameters was quantified for CL (44.3%), V(c) (25.5%), Q (44.6%), and V(p) (44.6%). Residual variability was estimated to be 15.0%. Body weight was found to be an important covariate on V(c). Golimumab was generally well tolerated. The pharmacokinetics of golimumab appeared to be linear over the dose range evaluated in this study.

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“…In contrast to the significant interaction in our clinical study with the herbal antidepressant St John's wort and docetaxel , E. purpurea did not significantly affect systemic exposure to docetaxel in the present study. Intraindividual changes in AUC (Figure ) were in line with an estimated intraindividual variability in docetaxel clearance of 25% . There are no clear explanations for the more remarkable 93% increase in AUC 0–∞ in one patient.…”

Section: Discussionmentioning

confidence: 71%

The effect of Echinacea purpurea on the pharmacokinetics of docetaxel

Goey

Meijerman

Rosing

et al. 2013

Brit J Clinical Pharma

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AIMSThe herbal medicine Echinacea purpurea (E. purpurea) has been shown to induce cytochrome P450 3A4 (CYP3A4) both in vitro and in humans. This study explored whether E. purpurea affects the pharmacokinetics of the CYP3A4 substrate docetaxel in cancer patients. METHODSTen evaluable cancer patients received docetaxel (135 mg, 60 min IV infusion) before intake of a commercially available E. purpurea extract (20 oral drops three times daily) and 3 weeks later after a 14 day supplementation period with E. purpurea. In both cycles, pharmacokinetic parameters of docetaxel were determined. RESULTSBefore and after supplementation with E. purpurea, the mean area under the plasma concentration-time curve of docetaxel was 3278 ± 1086 and 3480 ± 1285 ng ml −1 h, respectively. This result was statistically not significant. Nonsignificant alterations were also observed for the elimination half-life (from 30.8 ± 19.7 to 25.6 ± 5.9 h, P = 0.56) and maximum plasma concentration of docetaxel (from 2224 ± 609 to 2097 ± 925 ng ml −1 , P = 0.30).

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Population pharmacokinetics of docetaxel during phase I studies using nonlinear mixed-effect modeling and nonparametric maximum-likelihood estimation

Cited by 7 publications

References 0 publications

A physiologically based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer

A physiologically based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer

Pharmacokinetics and Safety of Golimumab, a Fully Human Anti‐TNF‐α Monoclonal Antibody, in Subjects With Rheumatoid Arthritis

The effect of Echinacea purpurea on the pharmacokinetics of docetaxel

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