PMID- 7834963
OWN - NLM
STAT- MEDLINE
DCOM- 19950302
LR  - 20220330
IS  - 0312-5963 (Print)
IS  - 0312-5963 (Linking)
VI  - 27
IP  - 4
DP  - 1994 Oct
TI  - Clinical pharmacokinetics of paclitaxel.
PG  - 256-69
AB  - Paclitaxel is a new anticancer agent showing significant promise as therapy for 
      solid tumours and leukaemia, given alone or in combination with other 
      chemotherapeutic agents. Paclitaxel concentrations in biological specimens can be 
      measured using high performance liquid chromatography, or more recently by 
      immunoassay. Pharmacokinetic studies in which adults have been administered 
      pacliaxel intravenously over 1 to 96 hours have demonstrated the following 
      pharmacokinetic characteristics: extensive tissue distribution; high plasma 
      protein binding (approximately 90 to 95%); variable systemic clearance, with 
      average clearances ranging from 87 to 503 ml/min/m2 (5.2 to 30.2 L/h/m2); and 
      minimal renal excretion of parent drug (< 10%). In vitro and in vivo studies have 
      demonstrated that paclitaxel is extensively metabolised by the liver to 3 primary 
      metabolites. Cytochrome P450 enzymes of the CYP3A and CYP2C subfamilies appear to 
      be involved in hepatic metabolism of paclitaxel. Although early reports suggested 
      that paclitaxel has first-order pharmacokinetics, some recent trials in children 
      and adults suggest that its elimination is saturable. The clinical importance of 
      saturable elimination would be greatest when large dosages are administered 
      and/or the drug is infused over a shorter period of time. In these situations, 
      achievable plasma concentrations are likely to exceed the affinity constant for 
      elimination (Km). Thus, small changes in dosage or infusion duration may result 
      in disproportionately large alterations in paclitaxel systemic exposure, 
      potentially influencing patient response. A pharmacokinetic analysis of the 
      combination of cisplatin and paclitaxel has demonstrated that paclitaxel 
      clearance is apparently sequence dependent. Patients administered cisplatin prior 
      to paclitaxel had lower clearances and greater clinical toxicity than patients 
      receiving paclitaxel before cisplatin. Additional pharmacodynamic analyses have 
      shown nonhaematological and haematological toxicity to correlate better with 
      parameters of paclitaxel exposure (e.g. area under the plasma concentration-time 
      curve, duration of plasma concentrations exceeding 0.1 mumol/L) than with the 
      administered dosage.
FAU - Sonnichsen, D S
AU  - Sonnichsen DS
AD  - Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, 
      Memphis Tennessee.
FAU - Relling, M V
AU  - Relling MV
LA  - eng
GR  - CA 20180/CA/NCI NIH HHS/United States
GR  - CA 31566/CA/NCI NIH HHS/United States
GR  - CA 51001/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (Blood Proteins)
RN  - 0 (Dosage Forms)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Absorption
MH  - Adult
MH  - Blood Proteins/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Chromatography, High Pressure Liquid
MH  - Dosage Forms
MH  - Drug Administration Routes
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Immunoassay
MH  - Paclitaxel/administration & dosage/*pharmacokinetics/pharmacology
MH  - Protein Binding
MH  - Tissue Distribution
RF  - 46
EDAT- 1994/10/01 00:00
MHDA- 1994/10/01 00:01
CRDT- 1994/10/01 00:00
PHST- 1994/10/01 00:00 [pubmed]
PHST- 1994/10/01 00:01 [medline]
PHST- 1994/10/01 00:00 [entrez]
AID - 10.2165/00003088-199427040-00002 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 1994 Oct;27(4):256-69. doi: 10.2165/00003088-199427040-00002.