A Systematic Literature Review Approach to Estimate the Therapeutic Index of Selected Immunosuppressant Drugs After Renal Transplantation
Year: 2016
Type: review
Study design: Systematic Review
Abstract: BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence standards for approval of generic formulations. However, many immunosuppressant drugs do not have a well-defined therapeutic index (TI). METHODS: We sought to determine whether safety, efficacy, and pharmacokinetic data obtained from the medical literature through a comprehensive literature search could be used to estimate the TI of cyclosporine, tacrolimus, and sirolimus. In this analysis, we considered TI ≤2 as a criterion to define a drug as having an NTI. RESULTS: Published literature indicates that cyclosporine has a TI of 2-3, which falls just short of our criteria to be classified as having an NTI. We found sirolimus and tacrolimus to have a therapeutic range of 5-12 ng/mL and of 5-20 ng/mL, respectively, but were unable to calculate the TI. CONCLUSIONS: Although the current literature does not provide a clear indication that these drugs have an NTI, the routine use of therapeutic drug monitoring in clinical practice suggests that more stringent testing of their pharmacokinetic and pharmacodynamic properties should be performed before the approval of generic formulations.
Source: Therapeutic Drug Monitoring
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, U.S. Food and Drug Administration, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1102705159, G1468556634, G1735616026, Use of Physiologically-Based PK/PD Models to Streamline Drug Approvals, Institutional Training Grant in Pediatric Infectious Disease, Duke CTSA (Composite), G2829770695, G3008453, G5139652136, Physiologically-Based Pharmacokinetic Models for Optimal Drug Dosing in Children, Immunological biomarker studies in myasthenia gravis, G7378573625, Duke CTSA (Composite)
OpenAlex ID: W2560486801