{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:54:31Z","timestamp":1791089671233,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2006,10,16]],"date-time":"2006-10-16T00:00:00Z","timestamp":1160956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                  <jats:p>\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P\u2010glycoprotein (P\u2010gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P\u2010gp could be considered to result from genetic polymorphisms encoding their genes.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms of\n                          <jats:italic>CYP3A4<\/jats:italic>\n                          ,\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          and\n                          <jats:italic>MDR1<\/jats:italic>\n                          on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction\u2013restriction fragment length polymorphism for\n                          <jats:italic>CYP3A4<\/jats:italic>\n                          *\n                          <jats:italic>18A<\/jats:italic>\n                          ,\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>3<\/jats:italic>\n                          and\n                          <jats:italic>MDR1 C3435T.<\/jats:italic>\n                          Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose\u2010adjusted trough blood concentrations (C\n                          <jats:sub>0<\/jats:sub>\n                          ) were determined and compared among the different genotype groups.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          The frequency of the\n                          <jats:italic>CYP3A4<\/jats:italic>\n                          *\n                          <jats:italic>18A, CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>3<\/jats:italic>\n                          and\n                          <jats:italic>MDR1 C3435T<\/jats:italic>\n                          variant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose\u2010adjusted C\n                          <jats:sub>0<\/jats:sub>\n                          in\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>1\/<\/jats:italic>\n                          *\n                          <jats:italic>1<\/jats:italic>\n                          genotype subjects (\n                          <jats:italic>n<\/jats:italic>\n                          \u00a0=\u00a06) was 14.8\u00a0ng\/mL per mg per kg (range 11.1\u201326.8\u00a0ng\/mL per mg per kg), in\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>1\/<\/jats:italic>\n                          *\n                          <jats:italic>3<\/jats:italic>\n                          patients (\n                          <jats:italic>n<\/jats:italic>\n                          \u00a0=\u00a034) it was 23.7\u00a0ng\/mL per mg per kg (range 9.0\u201361.0\u00a0ng\/mL per mg per kg) and for\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>3\/<\/jats:italic>\n                          *\n                          <jats:italic>3<\/jats:italic>\n                          patients (\n                          <jats:italic>n<\/jats:italic>\n                          \u00a0=\u00a066) it was 26.4\u00a0ng\/mL per mg per kg (range 9.8\u201385.8\u00a0ng\/mL per mg per kg;\n                          <jats:italic>P\u00a0=<\/jats:italic>\n                          \u00a00.012, Kruskal\u2013Wallis test). Accordingly, cyclosporine dose\u2010adjusted C\n                          <jats:sub>0<\/jats:sub>\n                          was larger in CYP3A5 non\u2010expressors than expressors in the first week after renal transplantation. In addition, wild\u2010type homozygotes (\n                          <jats:italic>n<\/jats:italic>\n                          \u00a0=\u00a021) for\n                          <jats:italic>MDR1 C3435T<\/jats:italic>\n                          had a slight but significantly lower dose\u2010adjusted C\n                          <jats:sub>0<\/jats:sub>\n                          compared with heterozygotes (\n                          <jats:italic>n<\/jats:italic>\n                          \u00a0=\u00a058): 17.7 (10.3\u201360.8) versus 26.4 (9.0\u201367.3)\u00a0ng\/mL per mg per kg, respectively (\n                          <jats:italic>P\u00a0=<\/jats:italic>\n                          \u00a00.014, Mann\u2013Whitney\n                          <jats:italic>U<\/jats:italic>\n                          \u2010test).\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          In conclusion, the present study shows that genetic polymorphisms in\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with the\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>3<\/jats:italic>\n                          variant genotype require a low dose of cyclosporine to reach target levels compared with those with the\n                          <jats:italic>CYP3A5<\/jats:italic>\n                          *\n                          <jats:italic>1<\/jats:italic>\n                          allele.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1111\/j.1440-1681.2006.04492.x","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T02:43:00Z","timestamp":1161139380000},"page":"1093-1098","source":"Crossref","is-referenced-by-count":84,"title":["EFFECTS OF GENETIC POLYMORPHISMS OF\n                    <i>CYP3A4<\/i>\n                    ,\n                    <i>CYP3A5<\/i>\n                    AND\n                    <i>MDR1<\/i>\n                    ON CYCLOSPORINE PHARMACOKINETICS AFTER RENAL TRANSPLANTATION"],"prefix":"10.1111","volume":"33","author":[{"given":"Yong\u2010Fang","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong\u2010Qi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang\u2010Hua","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan\u2010Ping","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Hao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199907150-00011"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(02)85038-X"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200211000-00008"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1988.7.79"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S0021-9258(18)81632-5","article-title":"Cytochrome P\u2010450 hPCN3, a novel cytochrome P\u2010450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA\u2010expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine","volume":"264","author":"Aoyama T","year":"1989","journal-title":"J. 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