Abstract
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) displays nonlinear pharmacokinetics in humans. Both peak plasma paclitaxel concentrations and areas under the curve (AUCs) of the concentration versus time profiles will change disproportionately to changes in dose. Models that accurately describe the plasma paclitaxel profile contain two separate saturable processes, both described by Michaelis-Menten kinetics. Pharmacokinetic models using only linear components ultimately fail to describe adequately the disposition of paclitaxel in the body. The major toxicity of paclitaxel, neutropenia, appears to be related to the duration of time that plasma paclitaxel concentrations are at or above a threshold value. This relationship is well described by a sigmoid-E(max) (maximum effect) model. Neutropenia is not directly related to either peak paclitaxel plasma concentration or to paclitaxel areas under the curve. A relationship between therapeutic efficacy and paclitaxel disposition is, as yet, undefined.
| Original language | English |
|---|---|
| Pages (from-to) | 16-23 |
| Number of pages | 8 |
| Journal | Seminars in Oncology |
| Volume | 22 |
| Issue number | 3 SUPPL. 6 |
| Publication status | Published - 1995 |
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ASJC Scopus subject areas
- Oncology
Cite this
Paclitaxel pharmacokinetics and pharmacodynamics. / Kearns, C. M.; Gianni, L.; Egorin, M. J.
In: Seminars in Oncology, Vol. 22, No. 3 SUPPL. 6, 1995, p. 16-23.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Paclitaxel pharmacokinetics and pharmacodynamics
AU - Kearns, C. M.
AU - Gianni, L.
AU - Egorin, M. J.
PY - 1995
Y1 - 1995
N2 - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) displays nonlinear pharmacokinetics in humans. Both peak plasma paclitaxel concentrations and areas under the curve (AUCs) of the concentration versus time profiles will change disproportionately to changes in dose. Models that accurately describe the plasma paclitaxel profile contain two separate saturable processes, both described by Michaelis-Menten kinetics. Pharmacokinetic models using only linear components ultimately fail to describe adequately the disposition of paclitaxel in the body. The major toxicity of paclitaxel, neutropenia, appears to be related to the duration of time that plasma paclitaxel concentrations are at or above a threshold value. This relationship is well described by a sigmoid-E(max) (maximum effect) model. Neutropenia is not directly related to either peak paclitaxel plasma concentration or to paclitaxel areas under the curve. A relationship between therapeutic efficacy and paclitaxel disposition is, as yet, undefined.
AB - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) displays nonlinear pharmacokinetics in humans. Both peak plasma paclitaxel concentrations and areas under the curve (AUCs) of the concentration versus time profiles will change disproportionately to changes in dose. Models that accurately describe the plasma paclitaxel profile contain two separate saturable processes, both described by Michaelis-Menten kinetics. Pharmacokinetic models using only linear components ultimately fail to describe adequately the disposition of paclitaxel in the body. The major toxicity of paclitaxel, neutropenia, appears to be related to the duration of time that plasma paclitaxel concentrations are at or above a threshold value. This relationship is well described by a sigmoid-E(max) (maximum effect) model. Neutropenia is not directly related to either peak paclitaxel plasma concentration or to paclitaxel areas under the curve. A relationship between therapeutic efficacy and paclitaxel disposition is, as yet, undefined.
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M3 - Article
C2 - 7597430
AN - SCOPUS:0029044165
VL - 22
SP - 16
EP - 23
JO - Seminars in Oncology
JF - Seminars in Oncology
SN - 0093-7754
IS - 3 SUPPL. 6
ER -