FTY720, a Novel Immunomodulator in de Novo Kidney Transplant Patients: Pharmacokinetics and Exposure-Response Relationship
| Autor: | Chyi-Hung Hsu, Andrej Skerjanec, Hans-H. Neumayer, Robert Schmouder, Helio Tedesco, Klemens Budde, Edward S. Cole |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.medical_specialty Population Urology Models Biological Drug Administration Schedule Pharmacokinetics Sphingosine hemic and lymphatic diseases Internal medicine medicine Humans Pharmacology (medical) education Kidney transplantation Aged Pharmacology Volume of distribution education.field_of_study Dose-Response Relationship Drug Fingolimod Hydrochloride Maintenance dose business.industry Middle Aged medicine.disease Kidney Transplantation Dose–response relationship Endocrinology Propylene Glycols Cohort Cyclosporine Alkaline phosphatase Female business Immunosuppressive Agents |
| Zdroj: | The Journal of Clinical Pharmacology. 45:1268-1278 |
| ISSN: | 0091-2700 |
| Popis: | The pharmacokinetics, safety, and preliminary efficacy of FTY720, a novel immunomodulator, were examined in de novo renal transplant patients. Both noncompartmental and population methods were used to estimate pharmacokinetic estimates in the patients. The steady-state plasma concentrations of FTY720 increased in accordance with maintenance dose level, indicating linearity in clearance and volume of distribution over the 0.25- to 2.5-mg dose range. The pharmacokinetics of FTY720 in de novo renal transplant patients were characterized by the long terminal phase half-life of approximately 200 hours across doses, high volume of distribution (>3000 L), and low clearance (10.8 L/h). The intersubject variation of clearance was 55%, and the intrasubject variation of FTY720 concentrations was 28%. The population analysis revealed significant positive relationships between baseline alkaline phosphatase and clearance, as well as between baseline body weight on apparent volume of distribution. There was no relationship between FTY720 concentrations within a given FTY720 dose cohort and the rate of allograft rejection. |
| Databáze: | OpenAIRE |
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