title: Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data.
abstract: BACKGROUND
  While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5'-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power.
  
  
  METHODS
  We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used.
  
  
  RESULTS
  High intra-personal variability in raltegravir serum levels was seen. Comparable Cmax concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While Cmax seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC12 is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels.
  
  
  CONCLUSIONS
  We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations.
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany ; Interdisciplinary HIV Centre (IZAR), University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Spinner
authors.affiliation: TUM Medical School, Technische Universitaet Muenchen, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wille
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany ; Interdisciplinary HIV Centre (IZAR), University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schwerdtfeger
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Thies
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Tanase
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Von Figura
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Ismaningerstr 22, 81675 Munich, Germany.
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.affiliation: Department of Medicine II, Division of Infectious Diseases, University Of Wuerzburg Medical Center, Oberduerrbacherstr 6, 97080 Wuerzburg, Germany.
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Heinz
authors.affiliation: Department of Medicine II, Division of Infectious Diseases, University Of Wuerzburg Medical Center, Oberduerrbacherstr 6, 97080 Wuerzburg, Germany.
authors.forename: Hartwig Hf
authors.initials: HH
authors.lastname: Klinker
keywords: Chewed; HIV; Mycobacterium avium; Pharmacokinetic; Raltegravir