WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Malaria is widespread across some areas of the world, most of which also bear the brunt of the human immunodeficiency virus (HIV) pandemic, resulting in a high incidence of co-infection of both diseases.• Ritonavir, a HIV protease inhibitor, and quinine, an antimalarial agent effective against multidrug-resistant Plasmodium falciparum, are likely to be administered concurrently for treatment of patients with HIV and malaria.• Both drugs are metabolized to a significant extent by CYP3A4 and ritonavir is a potent inhibitor of this enzyme.
WHAT THIS STUDY ADDS• With increasing access to antiretroviral drugs, it is important that potential interactions between therapies for HIV and malaria infections are investigated.• In this study, concurrent administration of ritonavir with quinine was found to be associated with marked elevation in the plasma levels of the antimalarial and a pronounced decrease in plasma concentrations of 3-hydroxyquinine, the major metabolite of quinine.• There was also a modest but significant increase (P < 0.05) in plasma concentrations of ritonavir in the presence of quinine.
AIMSTo evaluate the pharmacokinetic interactions between ritonavir and quinine in healthy volunteers.
METHODSTen healthy volunteers were each given 600-mg single oral doses of quinine alone, ritonavir alone (200 mg every 12 h for 9 days), and quinine in combination with ritonavir, in a three-period pharmacokinetic nonrandomized sequential design study. Quinine was co-administered with the 15th dose of ritonavir. Blood samples collected at predetermined time intervals were analysed for ritonavir, quinine and its major metabolite, 3-hydroxyquinine, using a validated high-performance liquid chromatography method. ) of the metabolite. Similarly, quinine caused modest but significant increases (P < 0.01) in the Cmax, AUC and elimination T1/2 of ritonavir.
RESULTS
Concurrent ritonavir administration resulted in about fourfold increases in both the
CONCLUSIONSDownward dosage adjustment of quinine appears necessary when concurrently administered with ritonavir.
Recent investigations of hypoxia physiology in the naked mole rat have opened up an interesting line of research into the basic physiological and genomic alterations that accompany hypoxia survival. The extent to which such findings connect the effect of hypoxia to metabolic rate (O₂ consumption), core body temperature (Tb), and transcripts encoding the immediate early gene product (such as c-fos) under a constant ambient temperature (Ta) is not well known. We investigated this issue in the current study. Our first sets of experiments measured Tb and metabolic rates during exposure of naked mole rats to hypoxia over a constant Ta. Hypoxia significantly decreased metabolic rates in the naked mole rat. Although core Tb also decreased during hypoxia, the effect of hypoxia in suppressing core Tb was not significant. The second series of experiments revealed that c-fos protein and mRNA expression in the hippocampus neurons (CA1) increased in naked mole rats that were repeatedly exposed to 3% O₂ for 60 min per day for 5 days when compared to normoxia. Our findings provide evidence for the up-regulation of c-fos and suppression of metabolic rate in hypoxia tolerating naked mole rats under constant ambient temperature. Metabolic suppression and c-fos upregulation constitute part of the physiological complex associated with adaptation to hypoxia.
These methods further extend opportunities for conducting clinical pharmacokinetic studies in nursing mother-infant pairs, especially in resource-limited settings.
We investigated the effect of concurrent ingestion of Garcinia kola seed on the pharmacokinetics of quinine. In a randomized crossover study, 24 healthy Nigerian volunteers were assigned into two groups (A and B; n = 12 per group) on the basis of G. kola dose orally ingested. Each subject received 600mg quinine sulphate before and after ingesting 12.5g of G. kola once daily for seven days (Group A) or 12.5g twice daily for six days and once on the seventh day (Group B). Blood samples were collected and analyzed for plasma quinine and its metabolite, (3-hydroxyquinine) using a validated HPLC method. Concurrent administration of quinine with G. kola reduced quinine tmax by 48% (group A), mean Cmax by 19% and 26% in groups A and B, and slight reduction in mean AUC0–∞ of quinine in both groups. 3-hydroxyquinine Cmax also reduced by 29% and 32%; AUC0–∞ by 13% and 9% respectively. The point estimates of the T/R ratio of the geometric means for all Cmax obtained and only the AUC0–∞ at a higher dose of G. kola were outside the 80–125% bioequivalence range. In conclusion, an herb-drug interaction was noted with concurrent quinine and G. kola administration.
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