Reductions in Darunavir may be partially attenuated by the addition of pharmacokinetic enhancers, but until more human data exists, this combination should not be used.
Darunavir/Cobicistat versus Rifampin
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Study Design
This was an in vitro study were researchers took cryopreserved primary human hepatocytes and treated with either RIF (rifampin) alone or together with COBI (cobicistat) or were left untreated. Test compounds were replenished every day for a total of 72 hours. After this the cells were treated with DRV (darunavir) for one hour.
Resultant DRV concentrations were quantified using HPLC-UV. Apparent intrinsic clearance (CLint) of DRV was calculated, and expressed as the mean ± SD (μl/min/106 hepatocytes) of a total of three biological replicates.
Study Results
Control group cells were treated with DRV alone and exhibited a CLint of 13.2 ± 1.5μl/min. While following incubation with 10µM RIF, DRV CLint was increased to 20.5 ± 4.7 μl/min. 1.28 μM COBI was sufficient to overcome the effect of 10µM RIF reducing DRV CLint by -3% comparted to the control.
Regression analysis showed that that COBI concentrations were associated with a percentage inhibition of (β = 11.3, p = 0.001)
Study Conclusions
Studying findings suggested that RIF-induced increases in DRV CLint were overcome by co-administration with COBI. These show the relative impact of pharmacoenhancers in the presence of RIF.
The authors do not suggest the need for dose adjustments when using these agents together, and further human trials are needed. Until such time, use clinical judgement when these drugs are utilized concomitantly.
References
Roberts O, Back DJ, Khoo S, Owen A, Siccardi M. Interaction of darunavir/ritonavir and darunavir/cobicistat with rifampicin in vitro [abstract 459]. Conference On Retroviruses And Opportunistic Infections. Boston, MA, USA. 2016; February 2016.
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