Cisplatin Pharmacokinetics and Its Nephrotoxicity in Diabetic Rabbits
Background: This study was designed to investigate the relationship between the attenuation of cisplatin (CDDP)-induced nephrotoxicity in experimental diabetic rabbits and the plasma pharmacokinetics of the free ultrafilterable and total plasma platinum (Pt) levels. Methods: Two groups of age-matche...
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| Veröffentlicht in: | Chemotherapy (Basel) 2001-03, Vol.47 (2), p.128-135 |
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| description | Background: This study was designed to investigate the relationship between the attenuation of cisplatin (CDDP)-induced nephrotoxicity in experimental diabetic rabbits and the plasma pharmacokinetics of the free ultrafilterable and total plasma platinum (Pt) levels. Methods: Two groups of age-matched male New Zealand white rabbits were used; the first group consisted of rabbits with streptozotocin-induced diabetes (single i.v. bolus dose of streptozotocin of 65 mg/kg in citrate buffer, pH 4.6), and the second group of nondiabetic rabbits treated with the same volume of citrate buffer. Both groups were treated with CDDP (5 mg/kg, single i.v. bolus dose) 3 days after induction of the diabetic state in the first group. The plasma Pt levels were followed for 4 h after CDDP administration, in which the free ultrafilterable and total plasma Pt concentrations were determined by atomic absorption spectrometry. The pharmacokinetic parameters of free ultrafilterable plasma Pt were determined using a noncompartment pharmacokinetic model of analysis. Results: The total plasma Pt levels declined in a biphasic manner and were adequately described by a two-compartment model. No significant change was observed in the pharmacokinetics of either the free ultrafilterable or total plasma Pt levels in the diabetic group in comparison with the control nondiabetic group (p > 0.05). However, 4 h after CDDP administration, the total plasma Pt level of the nondiabetic group was significantly higher than that of the diabetic rabbits (p < 0.001). Indices of nephrotoxicity were determined 7 days after CDDP administration. The results revealed that the diabetic state protected against CDDP-induced nephrotoxicity. The nondiabetic rabbits exhibited highly significant elevations in the serum creatinine and urea levels and a decrease in the serum albumin level (p < 0.001) in comparison with the diabetic group. Conclusions: These findings might suggest that the reduction in CDDP-induced nephrotoxicity in diabetic rabbits is not due to a change in the plasma pharmacokinetic profile within the drug follow-up period. It could be anticipated that the rapid decline in the total plasma Pt level after CDDP administration to diabetic rabbits, as well as the reduction in the terminal elimination half-life of the total plasma Pt level might be responsible for the reduction in CDDP-induced nephrotoxicity. Also, alterations in the how kidneys of diabetics deal with the renal excretion of Pt and reducti |
| doi_str_mv | 10.1159/000048512 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_karge</sourceid><recordid>TN_cdi_proquest_journals_223272618</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>677085061</sourcerecordid><originalsourceid>FETCH-LOGICAL-c449t-83426b97dc87095976a70310e5acf722e0fa1a99d62abe739cf4fe0b416357fb3</originalsourceid><addsrcrecordid>eNpt0EFLwzAUB_AgipvTg2dBip48VPOStGmOUqcbDBXRc0nTxGVubU06cN_ezI3tYi4hLz_-7_EQOgd8C5CIOxwOyxIgB6gPjEAsuGCHqB_KIqaQ8B468X4WnjSlcIx6AMBpBkkfDXPr27nsbB29TqVbSNV82Vp3VvlI1lU07nz0rNupa7rmxyrbraJAH6ws1yZ6k2VpO3-Kjoyce322vQfo43H4no_iycvTOL-fxIox0cUZZSQtBa9UxrFIBE8lxxSwTqQynBCNjQQpRJWSkM-pUIYZjUsGKU24KekAXW1yW9d8L7XvilmzdHVoWRBCCScpZAHdbJByjfdOm6J1diHdqgBcrPdV7PYV7OU2cFkudLWX2wUFcL0F0is5N07WyvqdyzjFTOzn-pLuU7vddz4a_vUp2soEdPEv2kzyC9QlhKw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>223272618</pqid></control><display><type>article</type><title>Cisplatin Pharmacokinetics and Its Nephrotoxicity in Diabetic Rabbits</title><source>MEDLINE</source><source>Karger Journals</source><creator>Najjar, Tawfeeg A.O. ; Saad, Sherif Y.</creator><creatorcontrib>Najjar, Tawfeeg A.O. ; Saad, Sherif Y.</creatorcontrib><description>Background: This study was designed to investigate the relationship between the attenuation of cisplatin (CDDP)-induced nephrotoxicity in experimental diabetic rabbits and the plasma pharmacokinetics of the free ultrafilterable and total plasma platinum (Pt) levels. Methods: Two groups of age-matched male New Zealand white rabbits were used; the first group consisted of rabbits with streptozotocin-induced diabetes (single i.v. bolus dose of streptozotocin of 65 mg/kg in citrate buffer, pH 4.6), and the second group of nondiabetic rabbits treated with the same volume of citrate buffer. Both groups were treated with CDDP (5 mg/kg, single i.v. bolus dose) 3 days after induction of the diabetic state in the first group. The plasma Pt levels were followed for 4 h after CDDP administration, in which the free ultrafilterable and total plasma Pt concentrations were determined by atomic absorption spectrometry. The pharmacokinetic parameters of free ultrafilterable plasma Pt were determined using a noncompartment pharmacokinetic model of analysis. Results: The total plasma Pt levels declined in a biphasic manner and were adequately described by a two-compartment model. No significant change was observed in the pharmacokinetics of either the free ultrafilterable or total plasma Pt levels in the diabetic group in comparison with the control nondiabetic group (p > 0.05). However, 4 h after CDDP administration, the total plasma Pt level of the nondiabetic group was significantly higher than that of the diabetic rabbits (p < 0.001). Indices of nephrotoxicity were determined 7 days after CDDP administration. The results revealed that the diabetic state protected against CDDP-induced nephrotoxicity. The nondiabetic rabbits exhibited highly significant elevations in the serum creatinine and urea levels and a decrease in the serum albumin level (p < 0.001) in comparison with the diabetic group. Conclusions: These findings might suggest that the reduction in CDDP-induced nephrotoxicity in diabetic rabbits is not due to a change in the plasma pharmacokinetic profile within the drug follow-up period. It could be anticipated that the rapid decline in the total plasma Pt level after CDDP administration to diabetic rabbits, as well as the reduction in the terminal elimination half-life of the total plasma Pt level might be responsible for the reduction in CDDP-induced nephrotoxicity. Also, alterations in the how kidneys of diabetics deal with the renal excretion of Pt and reduction of its accumulation in kidney tissue are not excluded.</description><identifier>ISSN: 0009-3157</identifier><identifier>EISSN: 1421-9794</identifier><identifier>DOI: 10.1159/000048512</identifier><identifier>PMID: 11173815</identifier><identifier>CODEN: CHTHBK</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Animals ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacokinetics ; Area Under Curve ; Biological and medical sciences ; Cisplatin - adverse effects ; Cisplatin - pharmacokinetics ; Creatinine - blood ; Diabetes Mellitus, Experimental - drug therapy ; Drug toxicity and drugs side effects treatment ; Experimental Chemotherapy ; Kidney Diseases - chemically induced ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Rabbits ; Toxicity: urogenital system ; Urea - blood</subject><ispartof>Chemotherapy (Basel), 2001-03, Vol.47 (2), p.128-135</ispartof><rights>2001 S. Karger AG, Basel</rights><rights>2001 INIST-CNRS</rights><rights>Copyright 2001 S. Karger AG, Basel</rights><rights>Copyright (c) 2001 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-83426b97dc87095976a70310e5acf722e0fa1a99d62abe739cf4fe0b416357fb3</citedby><cites>FETCH-LOGICAL-c449t-83426b97dc87095976a70310e5acf722e0fa1a99d62abe739cf4fe0b416357fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2428,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=873049$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11173815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Najjar, Tawfeeg A.O.</creatorcontrib><creatorcontrib>Saad, Sherif Y.</creatorcontrib><title>Cisplatin Pharmacokinetics and Its Nephrotoxicity in Diabetic Rabbits</title><title>Chemotherapy (Basel)</title><addtitle>Chemotherapy</addtitle><description>Background: This study was designed to investigate the relationship between the attenuation of cisplatin (CDDP)-induced nephrotoxicity in experimental diabetic rabbits and the plasma pharmacokinetics of the free ultrafilterable and total plasma platinum (Pt) levels. Methods: Two groups of age-matched male New Zealand white rabbits were used; the first group consisted of rabbits with streptozotocin-induced diabetes (single i.v. bolus dose of streptozotocin of 65 mg/kg in citrate buffer, pH 4.6), and the second group of nondiabetic rabbits treated with the same volume of citrate buffer. Both groups were treated with CDDP (5 mg/kg, single i.v. bolus dose) 3 days after induction of the diabetic state in the first group. The plasma Pt levels were followed for 4 h after CDDP administration, in which the free ultrafilterable and total plasma Pt concentrations were determined by atomic absorption spectrometry. The pharmacokinetic parameters of free ultrafilterable plasma Pt were determined using a noncompartment pharmacokinetic model of analysis. Results: The total plasma Pt levels declined in a biphasic manner and were adequately described by a two-compartment model. No significant change was observed in the pharmacokinetics of either the free ultrafilterable or total plasma Pt levels in the diabetic group in comparison with the control nondiabetic group (p > 0.05). However, 4 h after CDDP administration, the total plasma Pt level of the nondiabetic group was significantly higher than that of the diabetic rabbits (p < 0.001). Indices of nephrotoxicity were determined 7 days after CDDP administration. The results revealed that the diabetic state protected against CDDP-induced nephrotoxicity. The nondiabetic rabbits exhibited highly significant elevations in the serum creatinine and urea levels and a decrease in the serum albumin level (p < 0.001) in comparison with the diabetic group. Conclusions: These findings might suggest that the reduction in CDDP-induced nephrotoxicity in diabetic rabbits is not due to a change in the plasma pharmacokinetic profile within the drug follow-up period. It could be anticipated that the rapid decline in the total plasma Pt level after CDDP administration to diabetic rabbits, as well as the reduction in the terminal elimination half-life of the total plasma Pt level might be responsible for the reduction in CDDP-induced nephrotoxicity. Also, alterations in the how kidneys of diabetics deal with the renal excretion of Pt and reduction of its accumulation in kidney tissue are not excluded.</description><subject>Animals</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Area Under Curve</subject><subject>Biological and medical sciences</subject><subject>Cisplatin - adverse effects</subject><subject>Cisplatin - pharmacokinetics</subject><subject>Creatinine - blood</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Experimental Chemotherapy</subject><subject>Kidney Diseases - chemically induced</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Rabbits</subject><subject>Toxicity: urogenital system</subject><subject>Urea - blood</subject><issn>0009-3157</issn><issn>1421-9794</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0EFLwzAUB_AgipvTg2dBip48VPOStGmOUqcbDBXRc0nTxGVubU06cN_ezI3tYi4hLz_-7_EQOgd8C5CIOxwOyxIgB6gPjEAsuGCHqB_KIqaQ8B468X4WnjSlcIx6AMBpBkkfDXPr27nsbB29TqVbSNV82Vp3VvlI1lU07nz0rNupa7rmxyrbraJAH6ws1yZ6k2VpO3-Kjoyce322vQfo43H4no_iycvTOL-fxIox0cUZZSQtBa9UxrFIBE8lxxSwTqQynBCNjQQpRJWSkM-pUIYZjUsGKU24KekAXW1yW9d8L7XvilmzdHVoWRBCCScpZAHdbJByjfdOm6J1diHdqgBcrPdV7PYV7OU2cFkudLWX2wUFcL0F0is5N07WyvqdyzjFTOzn-pLuU7vddz4a_vUp2soEdPEv2kzyC9QlhKw</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>Najjar, Tawfeeg A.O.</creator><creator>Saad, Sherif Y.</creator><general>Karger</general><general>S. Karger AG</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20010301</creationdate><title>Cisplatin Pharmacokinetics and Its Nephrotoxicity in Diabetic Rabbits</title><author>Najjar, Tawfeeg A.O. ; Saad, Sherif Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-83426b97dc87095976a70310e5acf722e0fa1a99d62abe739cf4fe0b416357fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Area Under Curve</topic><topic>Biological and medical sciences</topic><topic>Cisplatin - adverse effects</topic><topic>Cisplatin - pharmacokinetics</topic><topic>Creatinine - blood</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Experimental Chemotherapy</topic><topic>Kidney Diseases - chemically induced</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Rabbits</topic><topic>Toxicity: urogenital system</topic><topic>Urea - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Najjar, Tawfeeg A.O.</creatorcontrib><creatorcontrib>Saad, Sherif Y.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><jtitle>Chemotherapy (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Najjar, Tawfeeg A.O.</au><au>Saad, Sherif Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cisplatin Pharmacokinetics and Its Nephrotoxicity in Diabetic Rabbits</atitle><jtitle>Chemotherapy (Basel)</jtitle><addtitle>Chemotherapy</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>47</volume><issue>2</issue><spage>128</spage><epage>135</epage><pages>128-135</pages><issn>0009-3157</issn><eissn>1421-9794</eissn><coden>CHTHBK</coden><abstract>Background: This study was designed to investigate the relationship between the attenuation of cisplatin (CDDP)-induced nephrotoxicity in experimental diabetic rabbits and the plasma pharmacokinetics of the free ultrafilterable and total plasma platinum (Pt) levels. Methods: Two groups of age-matched male New Zealand white rabbits were used; the first group consisted of rabbits with streptozotocin-induced diabetes (single i.v. bolus dose of streptozotocin of 65 mg/kg in citrate buffer, pH 4.6), and the second group of nondiabetic rabbits treated with the same volume of citrate buffer. Both groups were treated with CDDP (5 mg/kg, single i.v. bolus dose) 3 days after induction of the diabetic state in the first group. The plasma Pt levels were followed for 4 h after CDDP administration, in which the free ultrafilterable and total plasma Pt concentrations were determined by atomic absorption spectrometry. The pharmacokinetic parameters of free ultrafilterable plasma Pt were determined using a noncompartment pharmacokinetic model of analysis. Results: The total plasma Pt levels declined in a biphasic manner and were adequately described by a two-compartment model. No significant change was observed in the pharmacokinetics of either the free ultrafilterable or total plasma Pt levels in the diabetic group in comparison with the control nondiabetic group (p > 0.05). However, 4 h after CDDP administration, the total plasma Pt level of the nondiabetic group was significantly higher than that of the diabetic rabbits (p < 0.001). Indices of nephrotoxicity were determined 7 days after CDDP administration. The results revealed that the diabetic state protected against CDDP-induced nephrotoxicity. The nondiabetic rabbits exhibited highly significant elevations in the serum creatinine and urea levels and a decrease in the serum albumin level (p < 0.001) in comparison with the diabetic group. Conclusions: These findings might suggest that the reduction in CDDP-induced nephrotoxicity in diabetic rabbits is not due to a change in the plasma pharmacokinetic profile within the drug follow-up period. It could be anticipated that the rapid decline in the total plasma Pt level after CDDP administration to diabetic rabbits, as well as the reduction in the terminal elimination half-life of the total plasma Pt level might be responsible for the reduction in CDDP-induced nephrotoxicity. Also, alterations in the how kidneys of diabetics deal with the renal excretion of Pt and reduction of its accumulation in kidney tissue are not excluded.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>11173815</pmid><doi>10.1159/000048512</doi><tpages>8</tpages></addata></record> |
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| ispartof | Chemotherapy (Basel), 2001-03, Vol.47 (2), p.128-135 |
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| subjects | Animals Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Area Under Curve Biological and medical sciences Cisplatin - adverse effects Cisplatin - pharmacokinetics Creatinine - blood Diabetes Mellitus, Experimental - drug therapy Drug toxicity and drugs side effects treatment Experimental Chemotherapy Kidney Diseases - chemically induced Male Medical sciences Pharmacology. Drug treatments Rabbits Toxicity: urogenital system Urea - blood |
| title | Cisplatin Pharmacokinetics and Its Nephrotoxicity in Diabetic Rabbits |
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