Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer
Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in ma...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
1986 |
|---|
| Umfang: |
5 |
|---|
| Reproduktion: |
Springer Online Journal Archives 1860-2002 |
|---|---|
| Übergeordnetes Werk: |
in: Cancer chemotherapy and pharmacology - 1978, 18(1986) vom: März, Seite 247-251 |
| Übergeordnetes Werk: |
volume:18 ; year:1986 ; month:03 ; pages:247-251 ; extent:5 |
| Links: |
|---|
| Katalog-ID: |
NLEJ202994619 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLEJ202994619 | ||
| 003 | DE-627 | ||
| 005 | 20230505223646.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 070528s1986 xx |||||o 00| ||eng c | ||
| 035 | |a (DE-627)NLEJ202994619 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 245 | 1 | 0 | |a Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| 264 | 1 | |c 1986 | |
| 300 | |a 5 | ||
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. | ||
| 533 | |f Springer Online Journal Archives 1860-2002 | ||
| 700 | 1 | |a Rosenblum, Michael G. |4 oth | |
| 700 | 1 | |a Hortobagyi, Gabriel N. |4 oth | |
| 773 | 0 | 8 | |i in |t Cancer chemotherapy and pharmacology |d 1978 |g 18(1986) vom: März, Seite 247-251 |w (DE-627)NLEJ188987932 |w (DE-600)1458488-8 |x 1432-0843 |7 nnns |
| 773 | 1 | 8 | |g volume:18 |g year:1986 |g month:03 |g pages:247-251 |g extent:5 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/BF00273396 |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a ZDB-1-SOJ | ||
| 912 | |a GBV_NL_ARTICLE | ||
| 951 | |a AR | ||
| 952 | |d 18 |j 1986 |c 3 |h 247-251 |g 5 | ||
| matchkey_str |
article:14320843:1986----::hraoieisntsudsoiinfhbooiarsosmdfeby73cp |
|---|---|
| hierarchy_sort_str |
1986 |
| publishDate |
1986 |
| allfields |
(DE-627)NLEJ202994619 DE-627 ger DE-627 rakwb eng Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer 1986 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. Springer Online Journal Archives 1860-2002 Rosenblum, Michael G. oth Hortobagyi, Gabriel N. oth in Cancer chemotherapy and pharmacology 1978 18(1986) vom: März, Seite 247-251 (DE-627)NLEJ188987932 (DE-600)1458488-8 1432-0843 nnns volume:18 year:1986 month:03 pages:247-251 extent:5 http://dx.doi.org/10.1007/BF00273396 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 18 1986 3 247-251 5 |
| spelling |
(DE-627)NLEJ202994619 DE-627 ger DE-627 rakwb eng Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer 1986 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. Springer Online Journal Archives 1860-2002 Rosenblum, Michael G. oth Hortobagyi, Gabriel N. oth in Cancer chemotherapy and pharmacology 1978 18(1986) vom: März, Seite 247-251 (DE-627)NLEJ188987932 (DE-600)1458488-8 1432-0843 nnns volume:18 year:1986 month:03 pages:247-251 extent:5 http://dx.doi.org/10.1007/BF00273396 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 18 1986 3 247-251 5 |
| allfields_unstemmed |
(DE-627)NLEJ202994619 DE-627 ger DE-627 rakwb eng Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer 1986 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. Springer Online Journal Archives 1860-2002 Rosenblum, Michael G. oth Hortobagyi, Gabriel N. oth in Cancer chemotherapy and pharmacology 1978 18(1986) vom: März, Seite 247-251 (DE-627)NLEJ188987932 (DE-600)1458488-8 1432-0843 nnns volume:18 year:1986 month:03 pages:247-251 extent:5 http://dx.doi.org/10.1007/BF00273396 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 18 1986 3 247-251 5 |
| allfieldsGer |
(DE-627)NLEJ202994619 DE-627 ger DE-627 rakwb eng Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer 1986 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. Springer Online Journal Archives 1860-2002 Rosenblum, Michael G. oth Hortobagyi, Gabriel N. oth in Cancer chemotherapy and pharmacology 1978 18(1986) vom: März, Seite 247-251 (DE-627)NLEJ188987932 (DE-600)1458488-8 1432-0843 nnns volume:18 year:1986 month:03 pages:247-251 extent:5 http://dx.doi.org/10.1007/BF00273396 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 18 1986 3 247-251 5 |
| allfieldsSound |
(DE-627)NLEJ202994619 DE-627 ger DE-627 rakwb eng Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer 1986 5 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. Springer Online Journal Archives 1860-2002 Rosenblum, Michael G. oth Hortobagyi, Gabriel N. oth in Cancer chemotherapy and pharmacology 1978 18(1986) vom: März, Seite 247-251 (DE-627)NLEJ188987932 (DE-600)1458488-8 1432-0843 nnns volume:18 year:1986 month:03 pages:247-251 extent:5 http://dx.doi.org/10.1007/BF00273396 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 18 1986 3 247-251 5 |
| language |
English |
| source |
in Cancer chemotherapy and pharmacology 18(1986) vom: März, Seite 247-251 volume:18 year:1986 month:03 pages:247-251 extent:5 |
| sourceStr |
in Cancer chemotherapy and pharmacology 18(1986) vom: März, Seite 247-251 volume:18 year:1986 month:03 pages:247-251 extent:5 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| isfreeaccess_bool |
false |
| container_title |
Cancer chemotherapy and pharmacology |
| authorswithroles_txt_mv |
Rosenblum, Michael G. @@oth@@ Hortobagyi, Gabriel N. @@oth@@ |
| publishDateDaySort_date |
1986-03-01T00:00:00Z |
| hierarchy_top_id |
NLEJ188987932 |
| id |
NLEJ202994619 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ202994619</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230505223646.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">070528s1986 xx |||||o 00| ||eng c</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ202994619</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1986</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">5</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity.</subfield></datafield><datafield tag="533" ind1=" " ind2=" "><subfield code="f">Springer Online Journal Archives 1860-2002</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rosenblum, Michael G.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hortobagyi, Gabriel N.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">in</subfield><subfield code="t">Cancer chemotherapy and pharmacology</subfield><subfield code="d">1978</subfield><subfield code="g">18(1986) vom: März, Seite 247-251</subfield><subfield code="w">(DE-627)NLEJ188987932</subfield><subfield code="w">(DE-600)1458488-8</subfield><subfield code="x">1432-0843</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:18</subfield><subfield code="g">year:1986</subfield><subfield code="g">month:03</subfield><subfield code="g">pages:247-251</subfield><subfield code="g">extent:5</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://dx.doi.org/10.1007/BF00273396</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ZDB-1-SOJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_NL_ARTICLE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">18</subfield><subfield code="j">1986</subfield><subfield code="c">3</subfield><subfield code="h">247-251</subfield><subfield code="g">5</subfield></datafield></record></collection>
|
| series2 |
Springer Online Journal Archives 1860-2002 |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)NLEJ188987932 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| collection |
NL |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
1432-0843 |
| topic_title |
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
m g r mg mgr g n h gn gnh |
| hierarchy_parent_title |
Cancer chemotherapy and pharmacology |
| hierarchy_parent_id |
NLEJ188987932 |
| hierarchy_top_title |
Cancer chemotherapy and pharmacology |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)NLEJ188987932 (DE-600)1458488-8 |
| title |
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| spellingShingle |
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| ctrlnum |
(DE-627)NLEJ202994619 |
| title_full |
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| journal |
Cancer chemotherapy and pharmacology |
| journalStr |
Cancer chemotherapy and pharmacology |
| lang_code |
eng |
| isOA_bool |
false |
| recordtype |
marc |
| publishDateSort |
1986 |
| contenttype_str_mv |
zzz |
| container_start_page |
247 |
| container_volume |
18 |
| physical |
5 |
| format_se |
Elektronische Aufsätze |
| title_sort |
pharmacokinetics and tissue disposition of the biological response modifier bay i 7433 (copovithane) in patients with cancer |
| title_auth |
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| abstract |
Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. |
| abstractGer |
Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. |
| abstract_unstemmed |
Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. |
| collection_details |
GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE |
| title_short |
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer |
| url |
http://dx.doi.org/10.1007/BF00273396 |
| remote_bool |
true |
| author2 |
Rosenblum, Michael G. Hortobagyi, Gabriel N. |
| author2Str |
Rosenblum, Michael G. Hortobagyi, Gabriel N. |
| ppnlink |
NLEJ188987932 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth |
| up_date |
2024-07-06T09:29:33.334Z |
| _version_ |
1803821434363969536 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ202994619</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230505223646.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">070528s1986 xx |||||o 00| ||eng c</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ202994619</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1986</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">5</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2α of 11.1±4 min and a t1/2β of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity.</subfield></datafield><datafield tag="533" ind1=" " ind2=" "><subfield code="f">Springer Online Journal Archives 1860-2002</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rosenblum, Michael G.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hortobagyi, Gabriel N.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">in</subfield><subfield code="t">Cancer chemotherapy and pharmacology</subfield><subfield code="d">1978</subfield><subfield code="g">18(1986) vom: März, Seite 247-251</subfield><subfield code="w">(DE-627)NLEJ188987932</subfield><subfield code="w">(DE-600)1458488-8</subfield><subfield code="x">1432-0843</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:18</subfield><subfield code="g">year:1986</subfield><subfield code="g">month:03</subfield><subfield code="g">pages:247-251</subfield><subfield code="g">extent:5</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://dx.doi.org/10.1007/BF00273396</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ZDB-1-SOJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_NL_ARTICLE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">18</subfield><subfield code="j">1986</subfield><subfield code="c">3</subfield><subfield code="h">247-251</subfield><subfield code="g">5</subfield></datafield></record></collection>
|
| score |
7.3995686 |