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Primaquine decreased plasma concentration of ritonavir: single- and repeated-dose study in Sprague Dawley rats

By Melva Louisa, Vivian Soetikno, Nafrialdi Nafrialdi, Rianto Setiabudy and Frans D. Suyatna


<p><strong>Background:</strong> The present study was aimed to explore the effects of ritonavir and primaquine combination given as a singledose or repeated-dose compared to ritonavir alone on ritonavir plasma concentration in the rats.</p><p><strong>Methods:</strong> In single-dose study, 30 male Spraque Dawley rats were randomly allocated to receive ritonavir 20 mg/kg BW or ritonavir 20 mg/kg BW + primaquine 1.2 mg/kg BW or ritonavir 20 mg/kg BW + ketokonazole 10 mg/kg BW. Ketokonazole was used as positive control of ritonavir metabolism inhibitor. In the repeated-dose study, thirty Spraque Dawley male rats were randomly allocated to receive ritonavir 20 mg/kg BW/day or ritonavir 20 mg/kg BW/day + primaquine 1.2 mg/kg BW/day or ritonavir 20 mg/kg BW/day + rifampicin 100 mg/kg BW/day. Rifampicin was used as a positive control of ritonavir metabolism inducer.</p><p><strong>Results:</strong> In the single-dose study, ketokonazole increased the area under the plasma concentration (AUC) of ritonavir (↑114.8%, p&lt; 0.05), while primaquine tended to decrease the AUC of ritonavir (↓ 32.6%, p&gt; 0.05). Repeated-dose study showed that rifampicin decreases the AUC of ritonavir (↓ 42.8%, p&lt; 0.001), and primaquine decreased the AUC of ritonavir plasma concentration (↓ 46.6%, p&lt; 0.001).</p><p><strong>Conclusion:</strong> Concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect may result in the insufficient concentration of ritonavir as anti-HIV, which may lead to treatment failure with ritonavir. <em><strong>(Med J Indones 2011; 20:190-4)</strong></em></p><p><strong>Keywords:</strong> <em>drug interaction, metabolism, primaquine, ritonavir</em></p

Topics: Medicine (General), R5-920, Medicine, R
Publisher: Faculty of Medicine Universitas Indonesia
Year: 2011
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