title: Co-administration of ritonavir and primaquine decreases plasma concentration of primaquine: single- and multiple-dose study in the rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia. Jl. Salemba Raya no. 6, Jakarta Pusat 10430, Indonesia. melva.louisa@gmail.com
authors: Melva
authors: M
authors: Louisa
authors: Vivian
authors: V
authors: Soetikno
authors: Nafrialdi
authors: Rianto
authors: R
authors: Setiabudy
authors: Frans D
authors: FD
authors: Suyatna
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D000962:Antimalarials / Q000008:administration & dosage* / Q000097:blood*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000097:blood; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D011319:Primaquine / Q000008:administration & dosage* / Q000097:blood*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019438:Ritonavir / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000935:Antifungal Agents; D000962:Antimalarials; D017320:HIV Protease Inhibitors; D011319:Primaquine; D019438:Ritonavir; D007654:Ketoconazole