TY  - JOUR
A1  - Spinner, Christoph D
A1  - Wille, Florian
A1  - Schwerdtfeger, Christiane
A1  - Thies, Philipp
A1  - Tanase, Ursula
A1  - Von Figura, Guido
A1  - Schmid, Roland M
A1  - Heinz, Werner J
A1  - Klinker, Hartwig Hf
T1  - Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data
JF  - AIDS Research and Therapy
N2  - 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 C\(_{max}\) concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While C\(_{max}\) seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC(12) 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.
KW  - pharmacology
KW  - drug
KW  - HIV
KW  - chewed
KW  - Mycobacterium avium
KW  - raltegravir
KW  - pharmacokinetic
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144058
VL  - 12
IS  - 1
ER  -