2017
DOI: 10.1097/ftd.0000000000000364
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A Systematic Literature Review Approach to Estimate the Therapeutic Index of Selected Immunosuppressant Drugs After Renal Transplantation

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 th… Show more

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Cited by 20 publications
(11 citation statements)
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“…Our in vitro cell studies did not investigate the effect of TSC2+/+ immune cells or stromal cells on the TSC2-null cell growth. We believe inhibition of growth of human LAM cell organoids, in the presence or absence of different human immune or stromal cells, would be more clinically relevant using concentrations of rapamycin that are clinically tolerable, i.e., between 5-25 nM [20].…”
Section: Discussionmentioning
confidence: 99%
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“…Our in vitro cell studies did not investigate the effect of TSC2+/+ immune cells or stromal cells on the TSC2-null cell growth. We believe inhibition of growth of human LAM cell organoids, in the presence or absence of different human immune or stromal cells, would be more clinically relevant using concentrations of rapamycin that are clinically tolerable, i.e., between 5-25 nM [20].…”
Section: Discussionmentioning
confidence: 99%
“…Rapamycin was used at a concentration of 10 nM throughout our studies, since this is approximately the clinical blood concentration achieved in patients dosed once daily with 2 mg Sirolimus [8]. However, the pharmacokinetic/efficacy studies with Sirolimus were conducted in combination with other immunosuppressive drugs for transplantation patients with an effective dose range of 0.5-5 mg/day [20]. There has not been a comprehensive study of Sirolimus blood concentrations vs. efficacy in LAM patients.…”
Section: Lam Lung Cells Express Peif4e and Rapamycin Inhibits Ps6 Butmentioning
confidence: 99%
“…These are also called "critical-dose drugs" and often require therapeutic drug monitoring (TDM) and dose individualization based on patientspecific characteristics (Pater, 2004). Values of ≤2 (Bialer et al, 1998;Greenberg et al, 2016;Ericson et al, 2017) or ≤3 (Li et al, 2018) have been considered therapeutic index cut off points for NTI drugs. Examples of drugs that have been specified as NTI by regulatory agencies include anticoagulants (e.g., warfarin), antiarrhythmics (e.g., digoxin, flecainide), antiepileptics (e.g., phenytoin, carbamazepine), hormones (e.g., levothyroxine, ethinyl estradiol), and immunosuppressants (e.g., tacrolimus, sirolimus, cyclosporine) (Yu, 2011).…”
Section: Therapeutic Indexmentioning
confidence: 99%
“…This method performed by Ku and colleagues accurately determined the therapeutic index of phenytoin with data that had been collected from patients during standard care (Ku et al, 2016). Systematic review of published data has also been used to estimate the therapeutic index in approved drugs (Greenberg et al, 2016;Ericson et al, 2017). In these studies, safety, efficacy, and therapeutic monitoring data were gathered from published trials and successfully used to estimate the therapeutic index of antiepileptics (phenytoin, phenobarbital, and valproate) (Greenberg et al, 2016) and an immunosuppressant (cyclosporine) (Ericson et al, 2017).…”
Section: Therapeutic Indexmentioning
confidence: 99%
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