title: Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir.
abstract: OBJECTIVE
  The number of HIV-infected patients receiving orthotopic liver transplantation (OLTX) is increasing. One major challenge is the severe drug-drug interactions between immunosuppressive drugs such as tacrolimus and ritonavir-boosted HIV-1 protease inhibitors (PIs). The introduction of raltegravir, which is not metabolized by the cytochrome system, may allow concomitant treatment without dose adaptation.
  
  
  METHODS
  We conducted a retrospective analysis of HIV-1-infected patients receiving tacrolimus concomitantly with different HIV therapies, including 12 h pharmacokinetic assessment of drug levels.
  
  
  RESULTS
  Three OLTX patients received a ritonavir-boosted PI therapy when tacrolimus was added at very low doses of 0.06, 0.03 and 0.08 mg daily. Median tacrolimus blood levels were 6.6, 3.0 and 7.9 ng/mL over a follow-up period of 8, 22 and 33 months, respectively. In two other patients (one after OLTX and one with Crohn's disease), a raltegravir-based HIV therapy was started while patients received 1 or 2 mg of tacrolimus twice daily. No tacrolimus dose adjustment was necessary and drug levels remained unchanged.
  
  
  CONCLUSIONS
  Decreasing the dose of tacrolimus to 0.03-0.08 mg daily in patients with concomitant boosted PI therapy resulted in stable tacrolimus blood levels without alteration of PI drug levels. Concomitant use of raltegravir and tacrolimus revealed no clinically relevant drug interaction.
authors.affiliation: HIVCENTER, Goethe University Hospital, Theodor Stern Kai 7, 60590 Frankfurt, Germany. markusbickel@hotmail.com
authors.forename: Markus
authors.initials: M
authors.lastname: Bickel
authors.forename: Evrim
authors.initials: E
authors.lastname: Anadol
authors.forename: Martin
authors.initials: M
authors.lastname: Vogel
authors.forename: Wolf Peter
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Nils
authors.initials: N
authors.lastname: von Hentig
authors.forename: Johannes
authors.initials: J
authors.lastname: Kuetscher
authors.forename: Michael
authors.initials: M
authors.lastname: Kurowski
authors.forename: Christian
authors.initials: C
authors.lastname: Moench
authors.forename: Tessa
authors.initials: T
authors.lastname: Lennemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Lutz
authors.forename: Wolf Otto
authors.initials: WO
authors.lastname: Bechstein
authors.forename: Hans Reinhard
authors.initials: HR
authors.lastname: Brodt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044967:Serum / Q000737:chemistry; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D019380:Anti-HIV Agents; D007166:Immunosuppressive Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019438:Ritonavir; D016559:Tacrolimus