Jiang-Tao Tang1,2, Brenda C de Winter2, Dennis A Hesselink3, Ferdi Sombogaard4, Lan-Lan Wang1, Teun van Gelder2,3. 1. Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, China. 2. Department of Hospital Pharmacy, Clinical Pharmacology Unit, Erasmus MC, University Medical Center Rotterdam, The Netherlands. 3. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands. 4. Department of Hospital Pharmacy, VU Medical Center, Amsterdam, The Netherlands.
Abstract
AIMS: Elderly transplant recipients have a lower incidence of acute rejection, and a higher risk to die from infectious complications. A potential cause may be differences in the pharmacokinetics (PK) or pharmacodynamics (PD) of the immunosuppressive drugs they are taking. This study was designed to comprehensively evaluate the influence of age on the PK and PD of mycophenolic acid (MPA). METHODS: In this study the PK and PD of MPA was studied in 26 elderly and 54 younger renal transplant recipients treated with mycophenolate mofetil and tacrolimus. Patients were sampled repetitively, both before and during the first 6 months after kidney transplantation. Age-related variability in MPA PK, baseline IMPDH activity, as well as MPA-induced IMPDH inhibition were studied. RESULTS: The IMPDH activity pre-transplantation did not differ between elderly and younger patients. Neither IMPDH activity pre-transplantation nor maximum IMPDH inhibition was significantly correlated with the patients' age. The area under the MPA plasma concentration-time curve (AUC0-12h ) and the area under the effect (IMPDH activity)-time curve (AEC0-12h ) from 0 to 12 h were also not significantly different between the two groups. We found no significant differences in EC50 and Emax between elderly and younger patients. CONCLUSIONS: Age did not significantly affect the PK or PD of MPA. It is unlikely that the lower incidence of acute rejection in elderly patients, or the higher risk to die from a severe infection in elderly patients is due to different handling of MPA in the elderly.
AIMS: Elderly transplant recipients have a lower incidence of acute rejection, and a higher risk to die from infectious complications. A potential cause may be differences in the pharmacokinetics (PK) or pharmacodynamics (PD) of the immunosuppressive drugs they are taking. This study was designed to comprehensively evaluate the influence of age on the PK and PD of mycophenolic acid (MPA). METHODS: In this study the PK and PD of MPA was studied in 26 elderly and 54 younger renal transplant recipients treated with mycophenolate mofetil and tacrolimus. Patients were sampled repetitively, both before and during the first 6 months after kidney transplantation. Age-related variability in MPA PK, baseline IMPDH activity, as well as MPA-induced IMPDH inhibition were studied. RESULTS: The IMPDH activity pre-transplantation did not differ between elderly and younger patients. Neither IMPDH activity pre-transplantation nor maximum IMPDH inhibition was significantly correlated with the patients' age. The area under the MPA plasma concentration-time curve (AUC0-12h ) and the area under the effect (IMPDH activity)-time curve (AEC0-12h ) from 0 to 12 h were also not significantly different between the two groups. We found no significant differences in EC50 and Emax between elderly and younger patients. CONCLUSIONS: Age did not significantly affect the PK or PD of MPA. It is unlikely that the lower incidence of acute rejection in elderly patients, or the higher risk to die from a severe infection in elderly patients is due to different handling of MPA in the elderly.
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