Phase I study of single‐dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients

Autor: Daniel I. Feig, Martin Polinsky, Vidya Perera, Vikas R. Dharnidharka, Bindu Murthy, Mustimbo Roberts, Robert Ettenger, Barry L. Warshaw, Asha Moudgil
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Kidney Disease
kidney transplantation/nephrology
Medical and Health Sciences
Kidney transplant
Immunology and Allergy
Medicine
Pharmacology (medical)
immunosuppressant - fusion proteins and monoclonal antibodies
Child
belatacept
Volume of distribution
simulation
practice
Phase i study
Infectious Diseases
6.1 Pharmaceuticals
Area Under Curve
Female
pharmacokinetics/pharmacodynamics
Brief Communications
pharmacokinetics
Immunosuppressive Agents
medicine.drug
medicine.medical_specialty
Adolescent
Clinical Trials and Supportive Activities
Renal and urogenital
nephrology
Cmax
Urology
kidney transplantation
living donor
immunosuppressant ‐ fusion proteins and monoclonal antibodies
Brief Communication
clinical research/practice
Belatacept
Abatacept
Pharmacokinetics
Clinical Research
pharmacodynamics
Humans
Adverse effect
Transplantation
business.industry
Evaluation of treatments and therapeutic interventions
Organ Transplantation
Calcineurin
Surgery
business
Zdroj: American Journal of Transplantation
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol 19, iss 4
ISSN: 1600-6143
1600-6135
Popis: Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12‐17 years receiving a stable calcineurin inhibitor–based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein‐Barr virus were enrolled; all completed the 6‐month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [C max] and area under the serum concentration‐time curve from time zero extrapolated to infinity [AUC 0‐ INF] were 20% and 25%, respectively). Mean half‐life (T 1/2) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady‐state (V ss) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.
Results from a phase I study of adolescent renal transplant recipients administered a single intravenous infusion of belatacept at 7.5 mg/kg show comparable pharmacokinetic and pharmacodynamic values to those obtained historically from healthy adult volunteers given a single dose of belatacept (10 mg/kg) and adult kidney transplant recipients administered multiple doses of belatacept (5mg/kg/dose).
Databáze: OpenAIRE
Externí odkaz: