title: Trimethoprim-sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant recipients.
abstract: OBJECTIVE
  The influence of the trimethoprim-sulphamethoxazole combination on the steady-state pharmacokinetics of sirolimus, a potent macrocyclic immunosuppressant, was studied in renal transplant recipients.
  
  
  METHODS
  Fifteen kidney transplant recipients were treated with sirolimus 8-23 mg m(-2) in combination with azathioprine and prednisolone from the day of transplantation. Whole blood sirolimus AUC and C(max) were determined on days 6 and 7 after transplantation. On day 7, sirolimus was coadministered with the first dose of trimethoprim (80 mg) and sulphamethoxazole (400 mg).
  
  
  RESULTS
  On day 6, the mean (95% confidence interval) whole blood sirolimus AUC((0-24 h)) was 1040 (846, 1234) ng ml(-1) and mean C(max) was 109 (88, 129) ng ml(-1). Corresponding values on day 7 were AUC((0-24 h)) 1060 (826, 1293) ng ml(-1) and C(max) mean 107 (87, 127) ng ml(-1). The mean difference in the dose-corrected AUC((0-24 h)) was 0.40% (-9.4, +10).
  
  
  CONCLUSIONS
  A single dose of trimethoprim-sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant patients.
authors.affiliation: Department of Clinical Pharmacology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. ylva.boettiger@labmed.ki.se
authors.forename: Ylva
authors.initials: Y
authors.lastname: Böttiger
authors.forename: Christina
authors.initials: C
authors.lastname: Brattström
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
authors.forename: Kerstin
authors.initials: K
authors.lastname: Claesson
authors.forename: James T
authors.initials: JT
authors.lastname: Burke
mesh_terms: D000328:Adult; D000368:Aged; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D020123:Sirolimus / Q000493:pharmacokinetics*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000892:Anti-Infective Agents, Urinary; D007166:Immunosuppressive Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D020123:Sirolimus