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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-9-30
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pubmed:abstractText |
Doxorubicin pharmacokinetics were determined in 33 patients with solid tumours who received intravenous doses of 20-320 mg m(-2) HPMA copolymer bound doxorubicin (PK1) in a phase I study. Since assay constraints limited the data at lower doses, conventional analysis was not feasible and a 'population approach' was used. Bound concentrations were best described by a biexponential model and further analyses revealed a small influence of dose or weight on V1 but no identifiable effects of age, body surface area, renal or hepatic function. The final model was: clearance (Q) 0.194 I h(-1); central compartment volume (V1) 4.48 x (1+0.00074 x dose (mg)) I; peripheral compartment volume (V2) 7.94 I; intercompartmental clearance 0.685 I h(-1). Distribution and elimination half-lives had median estimates of 2.7 h and 49 h respectively. Free doxorubicin was present at most sampling times with concentrations around 1000 times lower than bound doxorubicin values. Data were best described using a biexponential model and the following parameters were estimated: apparent clearance 180 I h-(-1); apparent V1 (I) 1450 x (1+0.0013 x dose (mg)), apparent V2 (I) 21 300 x (1-0.0013 x dose (mg)) x (1+2.95 x height (m)) and apparent Q 6950 I h(-1). Distribution and elimination half-lives were 0.13 h and 85 h respectively.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-2265458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-2946403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-7554038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-7752255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-7786822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-8068854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-8270974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-8387903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-8875345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-8877017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-9084455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-925881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-9443625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10487619-9696578
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
99-107
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10487619-Adult,
pubmed-meshheading:10487619-Aged,
pubmed-meshheading:10487619-Antineoplastic Agents,
pubmed-meshheading:10487619-Dose-Response Relationship, Drug,
pubmed-meshheading:10487619-Doxorubicin,
pubmed-meshheading:10487619-Drug Carriers,
pubmed-meshheading:10487619-Female,
pubmed-meshheading:10487619-Humans,
pubmed-meshheading:10487619-Male,
pubmed-meshheading:10487619-Middle Aged,
pubmed-meshheading:10487619-Neoplasms,
pubmed-meshheading:10487619-Polymethacrylic Acids
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pubmed:year |
1999
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pubmed:articleTitle |
Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumours.
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pubmed:affiliation |
Department of Medicine & Therapeutics, University of Glasgow, UK.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Clinical Trial, Phase I
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