Co-administration of Ritonavir and Primaquine Decreases Plasma Concentration of Primaquine: Single- and Multiple-dose Study in the Rats  

Oleh:

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

Jenis: Article from Journal - ilmiah nasional - terakreditasi DIKTI
Dalam koleksi: Acta Medica Indonesiana vol. 44 no. 4 (Oct. 2012), page 273-279.
Topik: Primaquine; ritonavir; drug interaction; metabolism.
Fulltext: Co-administration of Ritonavir and Primaquine.pdf (1.45MB)

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Perpustakaan FK Nomor Panggil: A02.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Aim: to explore the effects of ritonavir and primaquine combination given as a single-dose or multiple-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 primaquine 12.5 mg/kgBW or primaquine 12.5 mg/kgBW + ritonavir 10 mg/kgBW or primaquine 12.5 mg/kgBW + ketokonazole 10 mg/kgBW. Ketokonazole was used as positive control for inhibitor of primaquine metabolism. In the multiple-dose study, thirty Spraque Dawley male rats were randomly allocated to receive primaquine 12.5 mg/kgBW/day or primaquine 12.5 mg/ kgBW/day + ritonavir 10 mg/kgBW/day or primaquine 12.5 mg/kgBW/day + rifampicin 100 mg/kgBW/day. Rifampicin was used as a positive control for inducer of primaquine metabolism. Results: in the single-dose study, ketokonazole increases the area under the plasma concentration (AUC) of primaquine (h45.8%, p<0.000), while the ritonavir decreases the AUC of primaquine (i64.6%, p<0.000). Multiple-dose study shows that both rifampicin and ritonavir decreases the AUC of primaquine by 60.2% (p<0.000) and 67.7% (p<0.000), respectively. Conclusion: concomitant administration of primaquine and ritonavir decreases the AUC of ritonavir. This effect could result in the insufficient concentration of primaquine as anti-relapse therapy in malaria caused by Plasmodium vivax, which might lead to treatment failure with primaquine.

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