Sex differences in cyclosporine pharmacokinetics and ABCB1 gene expression in mononuclear blood cells in African American and Caucasian renal transplant recipients
| Autor: | Gregory E. Wilding, Rocco C. Venuto, Robin DiFrancesco, Nicolae Leca, Ryan T. Danison, Aijaz Gundroo, Julia Zack, Kathryn Gillis, Kathleen M. Tornatore, Kiran Dole, Daniel A. Brazeau |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Anti-Inflammatory Agents Gene Expression Pharmacology Peripheral blood mononuclear cell White People Mycophenolic acid Body Mass Index Sex Factors Pharmacokinetics Internal medicine medicine Humans Distribution (pharmacology) Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 Kidney transplantation Aged P-glycoprotein biology Middle Aged Mycophenolic Acid medicine.disease Kidney Transplantation Black or African American Endocrinology Pharmacodynamics Cyclosporine Leukocytes Mononuclear biology.protein Prednisone Female Body mass index Immunosuppressive Agents medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 53:1039-1047 |
| ISSN: | 0091-2700 |
| Popis: | Cyclosporine exhibits pharmacokinetic and pharmacodynamic variability in renal transplant recipients (RTR) attributed to P-glycoprotein (P-gp), an ABCB1 efflux transporter that influences bioavailability and intracellular distribution. Data on race and sex influences on P-gp in RTR are lacking. We investigated sex and race influences on cyclosporine pharmacokinetics and ABCB1 gene expression in peripheral blood mononuclear cells (PBMC). Fifty-four female and male African American and Caucasian stable RTR receiving cyclosporine and mycophenolic acid completed a 12-hour study. ABCB1 gene expression was assessed in PBMCs pre-dose and 4 hours after cyclosporine. Statistical analysis used mixed effects models on transformed, normalized ABCB1 expression and cyclosporine pharmacokinetics. Sex and race differences were observed for the dose-normalized area under the concentration curve (AUC0-12 /Dose) [P = .0004], apparent clearance [P = .0004] and clearance/body mass index (CL/BMI) [P = .027] with slowest clearance and greatest drug exposure in females. Sex and race differences were found pre-dose and 4 hours for ABCB1 [P |
| Databáze: | OpenAIRE |
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