Bioavailability of Thai generic lopinavir/ritonavir
23 August 2009. Related: Conference reports, PK Workshop 10th 2009.
Polly Clayden, HIV i-Base
A poster authored by J van der Lugt and coworkers from Thailand and the Netherlands described pharmacokinetic (PK) data and short-term safety of a generic lopinavir/ritonavir (LPV/r) 200/50mg formulation tablet. [1]
In this study, patients receiving PI based therapy with viral load <50 copies/mL were switched to generic LPV/r 400/100mg twice daily. Trough concentrations (Cmin) were measured prior to the switch in 16 patients receiving Kaletra and 4 weeks after the switch in all patients.
Plasma levels of LPV and RTV were measured using high performance liquid chromatography with a lower limit of quantification of 0.1mg/L for LPV and 0.045mg/L for RTV.
A group of 37 patients were evaluated in this study; their mean (SD) weight was 60.3 (11.8) kg and18 were women. Two patients discontinued the study medications due to intolerance.
The investigators reported the mean (SD) Cmin of LPV was 7.3 (1.8) mg/mL. None of the patients evaluated had subtherapeutic levels. They found no difference in LPV Cmin in patients receiving Kaletra before switching to the generic formulation of LPV/r, p=0.21. However, the Cmin of the generic RTV was higher than that reported for Kaletra, p=0.019. They found the coefficient of variation was 25% for the tablet formulation and 54% for the Kaletra. They noted that these values did not appear to be affected by food intake.
They concluded: These data support the efforts in scaling up access to generic second line treatment in middle and low income countries.
Comment
There are currently limited protease inhibitors available for second line treatment in low and middle-income countries. Although originator LPV/r (Kaletra/Aluvia) is the most common protease inhibitor in industrialised countries, generic LPV/r is not widely used in resource limited settings as there have been concerns about the quality (including studies by the originator company) and limited data. [2]
These data are reassuring, as is the FDA tentative approval in March this year of Indian generic versions of LPV/r manufactured by Aurobindo and Matrix Laboratories. [3]
Studies of a paediatric sprinkle formulation from Cipla are underway.
References:
- van der Lugt J et al. Bioavailability of generic lopinavir/ritonavir in HIV-1 infected individuals. 10th International Workshop on Clinical Pharmacology of HIV Therapy, 15-17 April 2009, Amsterdam. Abstract P_41.
- Garren KW et al. Bioavailability of Generic Ritonavir and Lopinavir/ritonavir Tablet Products in a Dog Model Abbott Laboratories, Abbott Park, IL. 2nd International Workshop on HIV Treatment, Pathogenesis and Prevention Research in Resource-Poor Settings, 20-23 May 2008, Dakar, Senegal.
- http://www.fda.gov/InternationalPrograms/FDA BeyondOurBordersForeignOffices/AsiaandAfrica/ucm119231.htm