Population Pharmacokinetics of Mycophenolic Acid in Senile Chinese Kidney Transplant Recipients

Wang, C.X.; Meng, Fanhang; Chen, L.Z.; Ren, Bin; Li, S.X.; Fei, J.G.; Qiu, Jian; Deng, Shijie; Li, J.; Chen, S.Y.

doi:10.1016/j.transproceed.2007.02.082

Cited by 18 publications

(20 citation statements)

References 12 publications

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“…(18–20) This present study includes CNI pharmacokinetics in 2553 adults (393 between 65–84 years of age), and we have found that increasing age resulted in a progressive decline in CNI clearance, even after adjustment for clinical factors. Older subjects received a median of 1 and 2 mg per day lower tacrolimus dose than middle and young aged adults, respectively.…”

Section: Discussionmentioning

confidence: 64%

“…We studied 348 young (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) Of the 34479 tacrolimus troughs, 411 were obtained during once daily dosing, 33 995 during twice daily dosing and 72 during three times daily administration. Of the 11 133 cyclosporine toughs, 28 troughs were obtained during once daily administrations, 11 092 during twice daily dosing and 12 during three times daily.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs

Jacobson

Schladt

Oetting

et al. 2012

American Journal of Transplantation

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The number of older adults undergoing kidney transplantation has increased, yet little is known about calcineurin inhibitor (CNI) metabolism in this group. We studied CNI troughs and doses to determine if there were age related differences in metabolism and dose requirements. We studied 348 young (18–34 years), 1831 middle (35–64 years) and 374 older (65–84 years) adult kidney transplant recipients enrolled in a 7-center prospective study. Troughs were obtained from each patient 2x/week in weeks 1–8 and 2x/month in months 3–6. A multivariable linear mixed model examined the effect of age on log dose and weight normalized troughs. Older recipients had higher normalized tacrolimus troughs than middle or young age adults despite receiving doses a median of 1–2 mg/day lower. Age and CYP3A5*1 genotype had the largest effect on tacrolimus troughs. Older recipients also had higher normalized cyclosporine troughs than middle or young adults despite receiving median doses 100 mg/day lower. After normalization for dose and weight, CNI troughs were more than 50% higher in older adults than young adults. These data support age related changes in CNI metabolism. Further studies are needed to determine optimal dosing of CNIs in the elderly.

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Section: Discussionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs

Jacobson

Schladt

Oetting

et al. 2012

American Journal of Transplantation

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“…Age could theoretically influence MPA disposition through alterations in protein binding, hepatic glucuronidation capacity and renal function [31,40,73,74]. Wang et al [75] studied the impact of age on pharmacokinetic parameters in Chinese renal transplant recipients. They found that when giving the same dose of MMF, the MPA area under the curve (AUC) was significantly lower in the elderly group (n = 24, 65.6 ± 3.6 years old) than in the younger control group (n = 24, 39.6 ± 14.3 years old), while there was no significant difference in peak concentrations or time to C max [75].…”

Section: Mycophenolate Mofetilmentioning

confidence: 99%

“…Wang et al [75] studied the impact of age on pharmacokinetic parameters in Chinese renal transplant recipients. They found that when giving the same dose of MMF, the MPA area under the curve (AUC) was significantly lower in the elderly group (n = 24, 65.6 ± 3.6 years old) than in the younger control group (n = 24, 39.6 ± 14.3 years old), while there was no significant difference in peak concentrations or time to C max [75]. Conflicting result were reported by Miura et al [63] who found no impact of age on dose-adjusted AUC 0-12 , C max , C 0 , and CL/F of MPA.…”

Section: Mycophenolate Mofetilmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients

Shi

Hesselink

Gelder

2015

Transplantation Reviews

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“…Studies assessing immunosuppressant pharmacokinetic disposition among older kidney, liver and heart recipients have yielded diverse results [4,20,21,22,23]. Despite age-related immunological and pharmacological changes, current immunosuppression protocols are similar in young and elderly persons [24].…”

Section: Introductionmentioning

confidence: 99%

Effect of Different Immunosuppressive Drugs on Immune Cells from Young and Old Healthy Persons

Welzl

Kern

Mayer³

et al. 2014

Gerontology

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Background: Life expectancy, as well as the average age of patients undergoing solid organ transplantation, increases constantly. Consequently, immunosuppressive therapy is no longer limited to young organ recipients. Objective: Here, we investigate how different types of immunosuppressive therapy, namely the calcineurin inhibitors cyclosporin A and tacrolimus, as well as the mTOR inhibitor rapamycin, affect the function of immune cells in young and elderly persons. Methods: Proliferation, cell viability, cytokine production (IL-2, IFN-γ), H₂O₂ production and telomere length of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMCs) of young (n = 13; median age 27 years) and old (n = 19; median age 71 years) healthy donors were analyzed. Results: The inhibition of proliferation was dampened in PBMCs from elderly donors, especially after incubation with rapamycin. All three immunosuppressive drugs inhibited the production of IL-2 equally well, whereas the production of IFN-γ was less well inhibited by rapamycin. Both calcineurin inhibitors increased H₂O₂ concentrations after stimulation with PHA and led to a shortening of telomeres in PBMCs from young and old individuals. Rapamycin had only minor effects on H₂O₂ production and telomere length. Conclusion: Our results demonstrate that the effects of immunosuppressive drugs on PBMCs differ between young and elderly persons. Calcineurin inhibitors compared to rapamycin have a more pronounced prosenescence effect. These data indicate that specific treatment regimens for the elderly might therefore be considered.

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Population Pharmacokinetics of Mycophenolic Acid in Senile Chinese Kidney Transplant Recipients

Cited by 18 publications

References 12 publications

Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs

Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs

Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients

Effect of Different Immunosuppressive Drugs on Immune Cells from Young and Old Healthy Persons

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