Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities
Abstract Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance immunosuppression and is dosed empirically in elderly kidney transplant recipients (KTRs) resulting in health inequities. Limited immunosuppressive pharmacokinetics are available comparing adult ages. This secondary analysis c...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13495 |
| _version_ | 1797828855849811968 |
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| author | Kathleen M. Tornatore Kristopher Attwood Rocco C. Venuto Brian Murray |
| author_facet | Kathleen M. Tornatore Kristopher Attwood Rocco C. Venuto Brian Murray |
| author_sort | Kathleen M. Tornatore |
| collection | DOAJ |
| description | Abstract Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance immunosuppression and is dosed empirically in elderly kidney transplant recipients (KTRs) resulting in health inequities. Limited immunosuppressive pharmacokinetics are available comparing adult ages. This secondary analysis compared TAC and MPA pharmacokinetics and adverse effects (AEs) among young, middle‐aged, and elderly Black and White KTRs. The 12‐h TAC and MPA pharmacokinetics with AE evaluation were conducted in 67 stable KTRs greater than or equal to 6 months post‐transplant. TAC regimens were adjusted to target troughs. MPA regimens were adjusted using clinical response. Participants were: young: less than or equal to 40 years; middle age: greater than 40 to 60 years, and elderly greater than 60 years. Noncompartmental pharmacokinetic analysis determined area under the concentration‐time curve 0–12 h (AUC0‐12h), clearance (CL), and CL/body mass index (BMI) with 0‐h troughs. MPA enterohepatic recirculation (EHR), MPA‐AUC6‐12h/MPA‐AUC0‐12h, and MPA glucuronide (MPAG)‐AUC0‐12h/MPA‐AUC0‐12h were determined. Univariate analysis of variance (ANOVA) was conducted using SAS version 9.4. No group differences were noted for estimated glomerular filtration rate, MPA, and TAC doses. EHR was reduced in elderly with decreased MPA‐AUC6‐12h/MPA‐AUC0‐12h (p = 0.049) and increased MPAG‐AUC0‐12h/MPA‐AUC0‐12h (p = 0.036). MPA troughs (p = 0.045) were reduced in the elderly. TAC CL/BMI (p = 0.043) was reduced in the elderly. For therapeutic MPA AUC0‐12h: 30–60 mg·h/L, 34.3% KTRs achieved this target with 55.2% greater than the therapeutic range. 77.6% KTR were in the TAC AUC0‐12h target: 100–190 ng·h/mL and 19.4% were below this range with no age relationship. In 44% young, 26% middle‐age and 7.8% elderly subjects achieved target AUC0‐12h for both medications (p = 0.036). Neurologic AEs were manifested in the elderly (p = 0.014). Immunosuppressive pharmacokinetics demonstrated age‐related differences with reduced TAC CL/BMI and MPA EHR and increased neurologic AE in the elderly. This immunosuppressive regimen may require age‐adjusted individualization to optimize allograft function. |
| first_indexed | 2024-04-09T13:11:05Z |
| format | Article |
| id | doaj.art-440f0d06625b4bc99627ccf84b92eb19 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-04-09T13:11:05Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-440f0d06625b4bc99627ccf84b92eb192023-05-12T07:05:38ZengWileyClinical and Translational Science1752-80541752-80622023-05-0116586187110.1111/cts.13495Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequitiesKathleen M. Tornatore0Kristopher Attwood1Rocco C. Venuto2Brian Murray3Transplantation Immunosuppressive Pharmacology Research Program, Translational Pharmacology Research Core, Department of Pharmacy Practice School of Pharmacy and Pharmaceutical Sciences University at Buffalo Buffalo New York USADepartment of Biostatistics, School of Public Health and Health Professions University at Buffalo Buffalo New York USADepartment of Medicine, School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USADepartment of Medicine, School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USAAbstract Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance immunosuppression and is dosed empirically in elderly kidney transplant recipients (KTRs) resulting in health inequities. Limited immunosuppressive pharmacokinetics are available comparing adult ages. This secondary analysis compared TAC and MPA pharmacokinetics and adverse effects (AEs) among young, middle‐aged, and elderly Black and White KTRs. The 12‐h TAC and MPA pharmacokinetics with AE evaluation were conducted in 67 stable KTRs greater than or equal to 6 months post‐transplant. TAC regimens were adjusted to target troughs. MPA regimens were adjusted using clinical response. Participants were: young: less than or equal to 40 years; middle age: greater than 40 to 60 years, and elderly greater than 60 years. Noncompartmental pharmacokinetic analysis determined area under the concentration‐time curve 0–12 h (AUC0‐12h), clearance (CL), and CL/body mass index (BMI) with 0‐h troughs. MPA enterohepatic recirculation (EHR), MPA‐AUC6‐12h/MPA‐AUC0‐12h, and MPA glucuronide (MPAG)‐AUC0‐12h/MPA‐AUC0‐12h were determined. Univariate analysis of variance (ANOVA) was conducted using SAS version 9.4. No group differences were noted for estimated glomerular filtration rate, MPA, and TAC doses. EHR was reduced in elderly with decreased MPA‐AUC6‐12h/MPA‐AUC0‐12h (p = 0.049) and increased MPAG‐AUC0‐12h/MPA‐AUC0‐12h (p = 0.036). MPA troughs (p = 0.045) were reduced in the elderly. TAC CL/BMI (p = 0.043) was reduced in the elderly. For therapeutic MPA AUC0‐12h: 30–60 mg·h/L, 34.3% KTRs achieved this target with 55.2% greater than the therapeutic range. 77.6% KTR were in the TAC AUC0‐12h target: 100–190 ng·h/mL and 19.4% were below this range with no age relationship. In 44% young, 26% middle‐age and 7.8% elderly subjects achieved target AUC0‐12h for both medications (p = 0.036). Neurologic AEs were manifested in the elderly (p = 0.014). Immunosuppressive pharmacokinetics demonstrated age‐related differences with reduced TAC CL/BMI and MPA EHR and increased neurologic AE in the elderly. This immunosuppressive regimen may require age‐adjusted individualization to optimize allograft function.https://doi.org/10.1111/cts.13495 |
| spellingShingle | Kathleen M. Tornatore Kristopher Attwood Rocco C. Venuto Brian Murray Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities Clinical and Translational Science |
| title | Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities |
| title_full | Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities |
| title_fullStr | Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities |
| title_full_unstemmed | Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities |
| title_short | Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities |
| title_sort | age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable black and white kidney transplant recipients implications for health inequities |
| url | https://doi.org/10.1111/cts.13495 |
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