Disease relevance of 3-hydroxyquinine

• Between the patients with and without recrudescences, there were no significant differences either in fever clearance time or parasite clearance time or in the overall pharmacokinetics of quinine and 3-hydroxyquinine [1].
• The mean ratio of quinine to 3-hydroxyquinine area under the plasma concentration-time curve (AUC) values in acute malaria was 12.03 compared with 6.92 during convalescence P = 0.01 [2].
• Pharmacokinetics of quinine and 3-hydroxyquinine in severe falciparum malaria with acute renal failure [3].

High impact information on 3-hydroxyquinine

• Coadministration with ketoconazole also decreased the mean area under the plasma concentration versus time curve (AUC) of 3-hydroxyquinine (from 28.4 to 19.7 micromol x h x L(-1); P < .001), whereas coadministration with fluvoxamine increased 3-hydroxyquinine AUC significantly (from 28.4 to 30.2 micromol x h x L(-1); P < .05) [4].
• There was a significant correlation (r = 0.986, P < .001) between the CYP3A contents and the formation rates of 3-hydroxyquinine in eight human liver microsomal samples [5].
• Plasma and urine samples were collected before quinine administration, and up to 48 h thereafter, then analysed by h.p.l.c. for both quinine and its CYP3A4-generated metabolite, 3-hydroxyquinine [6].
• Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway [7].
• Formation of 3-hydroxyquinine had the highest intrinsic clearance in human liver microsomes (mean +/- S.D.) of 11.0 +/- 4.6 micro l/min/mg [7].

Chemical compound and disease context of 3-hydroxyquinine

• RESULTS: During acute malaria infection, the systemic clearance of quinine, antipyrine and ICG and the biotransformation of quinine to 3-hydroxyquinine were all reduced significantly when compared with values during convalescence [2].

Biological context of 3-hydroxyquinine

• The formation kinetics of 3-hydroxyquinine, 2'-quininone, (10S)-11-dihydroxydihydroquinine, and (10R)-11-dihydroxydihydroquinine were investigated in human liver microsomes and in human recombinant-expressed CYP3A4 [7].

Anatomical context of 3-hydroxyquinine

• RESULTS: The mean apparent Km value for 3-hydroxyquinine formation was 83 +/- 19 (s.d.) microM, ranging from 57 microM to 123 microM in microsomes from ten human livers [8].

Associations of 3-hydroxyquinine with other chemical compounds

• Antimalarial activity and interactions between quinine, dihydroquinine and 3-hydroxyquinine against Plasmodium falciparum in vitro [9].

Gene context of 3-hydroxyquinine

• AIMS: Our previous studies using in vitro hepatic microsomal preparations suggested that the hepatic metabolism of quinine to form the major metabolite 3-hydroxyquinine is most likely catalysed by human P450 3A (CYP3A) [8].
• CONCLUSION: The reduction in quinine clearance in acute malaria results predominantly from a disease-induced dysfunction in hepatic mixed-function oxidase activity (principally CYP 3A) which impairs the conversion of quinine to its major metabolite, 3-hydroxyquinine [2].

Analytical, diagnostic and therapeutic context of 3-hydroxyquinine

• Plasma and urine samples were analyzed for both quinine and its main metabolite 3-hydroxyquinine with HPLC methods [4].
• Plasma and urine samples were collected before quinine intake and 16 h thereafter and analysed for quinine and 3-hydroxyquinine using high-performance liquid chromatography [10].

References