Tayyab S Diwan1, Alicia B Lichvar1, Abbie D Leino1, Alexander A Vinks2, Uwe Christians3, Adele R Shields1,4, Michael A Cardi4, Tsuyoshi Fukuda2, Tomoyuki Mizuno2, Tiffany Kaiser5, E Steve Woodle1, Rita R Alloway6. 1. Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 2. Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 3. Department of Anesthesiology, iC42 Clinical Research and Development, University of Colorado Denver, Aurora, CO, USA. 4. The Christ Hospital, Cincinnati, OH, USA. 5. Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 6. Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Abstract
BACKGROUND: Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics. METHODS: This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study. The purpose of this study was to assess single-dose PK of immediate-release tacrolimus (IR-TAC), extended-release tacrolimus (ER-TAC), and mycophenolic acid (MPA) in adult ESRD patients post-LSG. RESULTS:Twenty-three subjects were included in the 24-hour PK assessments. The ratio of geometric means between ER-TAC and IR-TAC was 103.5% (90% CI; 89.6%-119.6%) for AUC0-24 and 92.5% (90% CI; 80.4%-106.4%) for Cmax . PK parameters were similar between ER-TAC and IR-TAC, except for Cmin (P=.004) and Cmax (P=.04). MPA AUC0-24 was similar when given with either ER-TAC or IR-TAC (P=.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0-24 values vs those with CYP3A5*3/*3 (IR-TACP<.001; ER-TACP=.008). Genotype did not impact MPA PK. CONCLUSION: Dose modification of immunosuppressants post-LSG may not be necessary aside from standard therapeutic drug monitoring.
RCT Entities:
BACKGROUND: Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics. METHODS: This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study. The purpose of this study was to assess single-dose PK of immediate-release tacrolimus (IR-TAC), extended-release tacrolimus (ER-TAC), and mycophenolic acid (MPA) in adult ESRDpatients post-LSG. RESULTS: Twenty-three subjects were included in the 24-hour PK assessments. The ratio of geometric means between ER-TAC and IR-TAC was 103.5% (90% CI; 89.6%-119.6%) for AUC0-24 and 92.5% (90% CI; 80.4%-106.4%) for Cmax . PK parameters were similar between ER-TAC and IR-TAC, except for Cmin (P=.004) and Cmax (P=.04). MPA AUC0-24 was similar when given with either ER-TAC or IR-TAC (P=.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0-24 values vs those with CYP3A5*3/*3 (IR-TACP<.001; ER-TACP=.008). Genotype did not impact MPA PK. CONCLUSION: Dose modification of immunosuppressants post-LSG may not be necessary aside from standard therapeutic drug monitoring.
Authors: Jordana B Cohen; Mary Ann Lim; Colleen M Tewksbury; Samuel Torres-Landa; Jennifer Trofe-Clark; Peter L Abt; Noel N Williams; Kristoffel R Dumon; Simin Goral Journal: Surg Obes Relat Dis Date: 2019-06 Impact factor: 4.734