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

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Background: 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.

Methods: 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.

Results: In the single-dose study, ketokonazole increased the area under the plasma concentration (AUC) of ritonavir (↑114.8%, p< 0.05), while primaquine tended to decrease the AUC of ritonavir (↓ 32.6%, p> 0.05). Repeated-dose study showed that rifampicin decreases the AUC of ritonavir (↓ 42.8%, p< 0.001), and primaquine decreased the AUC of ritonavir plasma concentration (↓ 46.6%, p< 0.001).

Conclusion: 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.

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Detail Information

Series Title

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Call Number

medical journal of indonesia, 20 (3) 2011 : 190-19

Publisher

Jakarta : faculty of medicine, universitas indonesia., 2011

Collation

6p

Language

ISBN/ISSN

0853-1773

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Content Type

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Media Type

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Edition

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Subject(s)

Plasma
RITONAVIR
PRIMAQUIRE
RAT, SPRAGUE-DAWLEY

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