Evaluation of Renal Anionic Secretion Following Living-donor and Deceased-donor Renal Transplantation: A Clinical Pharmacokinetic Study of Cefoxitin Microdosing
Hari V. Kalluri, Puneet Sood, Wenchen Zhao, Parmjeet S. Randhawa, Amit D. Tevar, Sundaram Hariharan, Abhinav Humar, Raman Venkataramanan
Transplantation Direct October 26, 2020 DOI: 10.1097/txd.0000000000001001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Longitudinal Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | De novo kidney transplant recipients |
| Intervention | Cefoxitin |
| Dose | 200 mg |
| Duration | Within 14 days and beyond 90 days posttransplantation |
| Topics | Microdosing |
| Key findings | Cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients compared with historical healthy controls, with no longitudinal changes in OAT secretion or differences between living- and deceased-donor recipients. |
Abstract
Background. Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs). Methods. The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation. Results. No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls. Conclusions. These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.
Comparable studies
Other observational and cohort studies on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Microdosing psychedelics: personality, mental health, and creativity differences in microdosers Respondents recruited from online forums | 2019 | Observational study | |
| Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing Individuals planning a weekly microdosing regimen | 2021 | Prospective observational study | n = 81 |
| Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. More than a thousand individuals from 59 countries | 2019 | Observational cohort | n = 1,000 |
| Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls Psilocybin microdosers and non-microdosing comparators | 2022 | Naturalistic observational study | n = 1,133 |
| Nonlinear Pharmacokinetics of Oral Quinidine and Verapamil in Healthy Subjects: A Clinical Microdosing Study Healthy subjects | 2011 | Observational cohort |