Lopinavir pharmacokinetic profiles in HIV-infected patients during rifabutin-based anti-mycobacterial therapy.
OBJECTIVE
To evaluate the pharmacokinetic profile of ritonavir-boosted lopinavir in HIV-infected patients during rifabutin-based anti-mycobacterial therapy.


METHODS
A longitudinal, cross-over pharmacokinetic evaluation of lopinavir with and without rifabutin in HIV-infected subjects with mycobacterial disease was done. All received lopinavir/ritonavir (400/100 mg twice a day) + an adjusted rifabutin dose of 150 mg every other day. Twelve-hour lopinavir pharmacokinetic sampling occurred at 2 weeks (T1) and 6 weeks (T2) after starting combined therapy and 10 weeks after completion of adjusted rifabutin (T3). Plasma was assayed using an HPLC method; lopinavir plasma concentration-time data were analysed using non-compartmental methods.


RESULTS
In 10 patients with complete lopinavir curves at T1, T2 and T3 pharmacokinetic values were, respectively: AUC(0-12), 187.5, 161.8 and 121.1 μg · h/mL; C(trough), 13.2, 10.0 and 7.7 μg/mL; C(max), 18.7, 15.9 and 13.3 μg/mL; and apparent oral clearance (CL/F), 0.035, 0.037 and 0.045 L/h/kg. Lopinavir C(trough) and AUC(0-12) were significantly higher at T1 compared with T3 while CL/F remained unchanged throughout. Combined treatment was well tolerated and none of the patients experienced moderate to severe lopinavir-related adverse events.


CONCLUSIONS
Lopinavir serum concentrations are not reduced when the drug is administered together with an adjusted dose of 150 mg of rifabutin every other day.
Institute of Infectious and Tropical Diseases, Brescia University Hospital, Brescia, Italy. matteelli@med.unibs.it
Alberto
A
Matteelli
Paola
P
Villani
Anna Cristina C
AC
Carvalho
Issa
I
El-Hamad
Maria
M
Cusato
Alessandra
A
Apostoli
Claudio
C
Marcantoni
Alessandra
A
Calabresi
Sarah
S
Dal Zoppo
Sara
S
Bigoni
Mario
M
Regazzi
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D017828:Rifabutin / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D017828:Rifabutin; D061466:Lopinavir; D019438:Ritonavir