Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats
The present study examined the pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin (SNB-5001) in partially nephrectomized rats. The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-500...
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| Veröffentlicht in: | Folia Pharmacologica Japonica 1992, Vol.99(4), pp.205-211 |
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| creator | MASUNAGA, Hiroaki TAKAHIRA, Reiko KOHSAKA, Kazuhiro SAWAI, Tadanori |
| description | The present study examined the pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin (SNB-5001) in partially nephrectomized rats. The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-5001 (50 U/kg) in these rats showed a biexponential pattern similar to that in non-treated rats, conforming to a two-compartment model. However, the total body clearance was reduced, the plasma half life was prolonged and the area under the concentration-time curve of SNB-5001 was increased by the partial nephrectomy. The distribution volumes of SNB-5001 were almost the same as those in non-treated rats. It is suggested that the kidney may contribute to the elimination of SNB-5001. Dose-dependent increases of reticulocytes, red blood cells, hemoglobin and hematocrits were observed after seven repetitive intravenous injections of SNB-5001 in both partially nephrectomized rats and non-treated rats. Hemopoietic responses were calculated by subtracting the initial values from the values after SNB-5001 injections of each hematological parameter (reticulocytes, red blood cells, hemoglobin and hematocrits). Hemopoietic responses in partially nephrectomized rats were apparently stronger than those in non-treated rats. These results suggest that the reduction of clearance by the partial nephrectomy may contribute to the hemopoietic responses, in addition to suggesting that the uremic conditions do not inhibit the effects of SNB-5001 in partially nephrectomized rats. |
| doi_str_mv | 10.1254/fpj.99.205 |
| format | Article |
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The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-5001 (50 U/kg) in these rats showed a biexponential pattern similar to that in non-treated rats, conforming to a two-compartment model. However, the total body clearance was reduced, the plasma half life was prolonged and the area under the concentration-time curve of SNB-5001 was increased by the partial nephrectomy. The distribution volumes of SNB-5001 were almost the same as those in non-treated rats. It is suggested that the kidney may contribute to the elimination of SNB-5001. Dose-dependent increases of reticulocytes, red blood cells, hemoglobin and hematocrits were observed after seven repetitive intravenous injections of SNB-5001 in both partially nephrectomized rats and non-treated rats. Hemopoietic responses were calculated by subtracting the initial values from the values after SNB-5001 injections of each hematological parameter (reticulocytes, red blood cells, hemoglobin and hematocrits). Hemopoietic responses in partially nephrectomized rats were apparently stronger than those in non-treated rats. These results suggest that the reduction of clearance by the partial nephrectomy may contribute to the hemopoietic responses, in addition to suggesting that the uremic conditions do not inhibit the effects of SNB-5001 in partially nephrectomized rats.</description><identifier>ISSN: 0015-5691</identifier><identifier>EISSN: 1347-8397</identifier><identifier>DOI: 10.1254/fpj.99.205</identifier><identifier>PMID: 1607130</identifier><language>jpn</language><publisher>Japan: The Japanese Pharmacological Society</publisher><subject>Animals ; Dose-Response Relationship, Drug ; Erythropoietin - pharmacokinetics ; Erythropoietin - pharmacology ; Half-Life ; Hematopoiesis - drug effects ; Kidney - metabolism ; Male ; Nephrectomy ; Rats ; Rats, Inbred Strains ; Recombinant Proteins - pharmacokinetics ; Recombinant Proteins - pharmacology ; Uremia - metabolism</subject><ispartof>Folia Pharmacologica Japonica, 1992, Vol.99(4), pp.205-211</ispartof><rights>The Japanese PharmacologicalSociety</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1607130$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MASUNAGA, Hiroaki</creatorcontrib><creatorcontrib>TAKAHIRA, Reiko</creatorcontrib><creatorcontrib>KOHSAKA, Kazuhiro</creatorcontrib><creatorcontrib>SAWAI, Tadanori</creatorcontrib><title>Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats</title><title>Folia Pharmacologica Japonica</title><addtitle>Nihon Yakurigaku Zasshi</addtitle><description>The present study examined the pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin (SNB-5001) in partially nephrectomized rats. The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-5001 (50 U/kg) in these rats showed a biexponential pattern similar to that in non-treated rats, conforming to a two-compartment model. However, the total body clearance was reduced, the plasma half life was prolonged and the area under the concentration-time curve of SNB-5001 was increased by the partial nephrectomy. The distribution volumes of SNB-5001 were almost the same as those in non-treated rats. It is suggested that the kidney may contribute to the elimination of SNB-5001. Dose-dependent increases of reticulocytes, red blood cells, hemoglobin and hematocrits were observed after seven repetitive intravenous injections of SNB-5001 in both partially nephrectomized rats and non-treated rats. Hemopoietic responses were calculated by subtracting the initial values from the values after SNB-5001 injections of each hematological parameter (reticulocytes, red blood cells, hemoglobin and hematocrits). Hemopoietic responses in partially nephrectomized rats were apparently stronger than those in non-treated rats. These results suggest that the reduction of clearance by the partial nephrectomy may contribute to the hemopoietic responses, in addition to suggesting that the uremic conditions do not inhibit the effects of SNB-5001 in partially nephrectomized rats.</description><subject>Animals</subject><subject>Dose-Response Relationship, Drug</subject><subject>Erythropoietin - pharmacokinetics</subject><subject>Erythropoietin - pharmacology</subject><subject>Half-Life</subject><subject>Hematopoiesis - drug effects</subject><subject>Kidney - metabolism</subject><subject>Male</subject><subject>Nephrectomy</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Recombinant Proteins - pharmacokinetics</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Uremia - metabolism</subject><issn>0015-5691</issn><issn>1347-8397</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMGPEyEYxYnRrM26F-8mnIyaTIUywHB0m3U12ehBPRNKP5xZZ2AEeujVv9xv0qZ7AMJ773uBHyGvOVvzjWw_hvlxbcx6w-QzsuKi1U0njH5OVoxx2Uhl-EtyU8qwY0zqjVaCX5Errpjmgq3Iv7sQwNdCU6Czy3VwI40w9xnFNB1pirT2QOfe5cn59GeIUAdfqIv7i7g_RjctInbgXJp2Q3Sx0v4wuUghH2uf05wGnIz03Y9vt43Et72neMuullfkRXBjgZvzeU1-fb77uf3SPHy__7r99NB4YdraeL9THvbcSRNC5xkurkLHlWJGO_xN60FLzoQCqRGB6YyXAIq7VjMwRlyTt6feOae_ByjVTkPxMI4uQjoUqwUSkm2HwQ-noM-plAzBznmYXD5azuzC3CJza4xF5hh-c2497CbYP0VPhNHfnvzHUt1vuPgLaz_CUsVN2y515w1bL65HxBai-A9tGJXF</recordid><startdate>1992</startdate><enddate>1992</enddate><creator>MASUNAGA, Hiroaki</creator><creator>TAKAHIRA, Reiko</creator><creator>KOHSAKA, Kazuhiro</creator><creator>SAWAI, Tadanori</creator><general>The Japanese Pharmacological Society</general><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>7X8</scope></search><sort><creationdate>1992</creationdate><title>Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats</title><author>MASUNAGA, Hiroaki ; TAKAHIRA, Reiko ; KOHSAKA, Kazuhiro ; SAWAI, Tadanori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c394t-ccb6ced1a59ff8c0f8c16f8166097a7134ce751036e57839989c5ee61a470e993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>jpn</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Dose-Response Relationship, Drug</topic><topic>Erythropoietin - pharmacokinetics</topic><topic>Erythropoietin - pharmacology</topic><topic>Half-Life</topic><topic>Hematopoiesis - drug effects</topic><topic>Kidney - metabolism</topic><topic>Male</topic><topic>Nephrectomy</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Recombinant Proteins - pharmacokinetics</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Uremia - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MASUNAGA, Hiroaki</creatorcontrib><creatorcontrib>TAKAHIRA, Reiko</creatorcontrib><creatorcontrib>KOHSAKA, Kazuhiro</creatorcontrib><creatorcontrib>SAWAI, Tadanori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Folia Pharmacologica Japonica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MASUNAGA, Hiroaki</au><au>TAKAHIRA, Reiko</au><au>KOHSAKA, Kazuhiro</au><au>SAWAI, Tadanori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats</atitle><jtitle>Folia Pharmacologica Japonica</jtitle><addtitle>Nihon Yakurigaku Zasshi</addtitle><date>1992</date><risdate>1992</risdate><volume>99</volume><issue>4</issue><spage>205</spage><epage>211</epage><pages>205-211</pages><issn>0015-5691</issn><eissn>1347-8397</eissn><abstract>The present study examined the pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin (SNB-5001) in partially nephrectomized rats. The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-5001 (50 U/kg) in these rats showed a biexponential pattern similar to that in non-treated rats, conforming to a two-compartment model. However, the total body clearance was reduced, the plasma half life was prolonged and the area under the concentration-time curve of SNB-5001 was increased by the partial nephrectomy. The distribution volumes of SNB-5001 were almost the same as those in non-treated rats. It is suggested that the kidney may contribute to the elimination of SNB-5001. Dose-dependent increases of reticulocytes, red blood cells, hemoglobin and hematocrits were observed after seven repetitive intravenous injections of SNB-5001 in both partially nephrectomized rats and non-treated rats. Hemopoietic responses were calculated by subtracting the initial values from the values after SNB-5001 injections of each hematological parameter (reticulocytes, red blood cells, hemoglobin and hematocrits). Hemopoietic responses in partially nephrectomized rats were apparently stronger than those in non-treated rats. These results suggest that the reduction of clearance by the partial nephrectomy may contribute to the hemopoietic responses, in addition to suggesting that the uremic conditions do not inhibit the effects of SNB-5001 in partially nephrectomized rats.</abstract><cop>Japan</cop><pub>The Japanese Pharmacological Society</pub><pmid>1607130</pmid><doi>10.1254/fpj.99.205</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Folia Pharmacologica Japonica, 1992, Vol.99(4), pp.205-211 |
| issn | 0015-5691 1347-8397 |
| language | jpn |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Dose-Response Relationship, Drug Erythropoietin - pharmacokinetics Erythropoietin - pharmacology Half-Life Hematopoiesis - drug effects Kidney - metabolism Male Nephrectomy Rats Rats, Inbred Strains Recombinant Proteins - pharmacokinetics Recombinant Proteins - pharmacology Uremia - metabolism |
| title | Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats |
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