Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy.
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.



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.



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 AUC0-24and 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 AUC0-24was similar when given with either ER-TAC or IR-TAC (P=.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0-24values vs those with CYP3A5*3/*3 (IR-TACP<.001; ER-TACP=.008). Genotype did not impact MPA PK.



Dose modification of immunosuppressants post-LSG may not be necessary aside from standard therapeutic drug monitoring.
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Tayyab S
TS
Diwan
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Alicia B
0000-0003-3804-6517
AB
Lichvar
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Abbie D
AD
Leino
Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Alexander A
AA
Vinks
Department of Anesthesiology, iC42 Clinical Research and Development, University of Colorado Denver, Aurora, CO, USA.
Uwe
U
Christians
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.|The Christ Hospital, Cincinnati, OH, USA.
Adele R
AR
Shields
The Christ Hospital, Cincinnati, OH, USA.
Michael A
MA
Cardi
Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Tsuyoshi
T
Fukuda
Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Tomoyuki
T
Mizuno
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Tiffany
T
Kaiser
Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
E Steve
ES
Woodle
Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Rita R
RR
Alloway
D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy / Q000009:adverse effects*; D006084:Graft Rejection / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D010535:Laparoscopy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing / Q000379:methods; D010865:Pilot Projects; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D014018:Tissue Distribution
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A
laparoscopic sleeve gastrectomy; mycophenolic acid; pharmacogenomics; pharmacokinetics; tacrolimus