Dosing rifabutin and lopinavir/r sub-optimal rifabutin levels reported in five patients dosed according to current guidelines
Simon Collins, HIV i-Base
Hasanin Khachi and colleagues from Barts and the London Trust reported drug levels of rifabutin in five patients concurrently using lopinavir/r-based ARV regimens. Following current guidelines (BHIVA, CDC), rifabutin dose was reduced from 300mg daily to 150mg three times a week, in five patients, and levels were measured using standard therapeutic drug monitoring after two weeks.
Rifabutin levels for all five patients were sub-therapeutic, (see Table 1) with one patient deteriorating clinically.
The researchers concluded that this data suggests current BHIVA and CDC guidelines result in sub-therapeutic rifabutin levels and that further formal investigations are required to establish the clinical significance of this, and determine the optimum dosing regimes for Kaletra and rifabutin in co-infected patients.
Table 1: Rifabutin levels at week 2
|Patient||Rifabution 4h post-level (mg/L)||Kaletra trough level (ng/mL)|
Rifabutin post-dose: 0.50-1.0 mg/L
Kaletra trough level: for wild type virus: 1000 ng/L
*Experienced patients: 8000 ng/L
Khachi H, Ladenheim D, Orkin C et al. Pharmacokinetic interactions between rifabutin and lopinavir/ritonavir in HIV-infected patients with mycobacterial co-infection. Oral abstract O12.