The incidence of poor metabolizer phenotypes for debrisoquine (CYP2D6) in South Pacific Polynesians appears to lower than in Caucasian populations, while the prevalence of poor metabolizers for proguanil (CYP2C19) in this ethnic population is higher. The frequencies of the poor metabolizer phenotype for debrisoquine and also for proguanil in South Pacific Polynesians are similar to those reported in Asian populations.
The effect of age on the pharmacokinetics of quinine was investigated by comparing its kinetic behaviour in 12 young healthy adults and 8 healthy elderly subjects after a single 600 mg oral dose of quinine sulphate. Peak plasma quinine concentration and the time of peak concentration were similar in the young and elderly subjects. The mean oral clearance of quinine was found to be significantly decreased in the elderly (P less than 0.05, 0.062 litre/h/kg vs 0.084 litre/h/kg) as compared to the young. This was accompanied by a significant increase in the mean elimination half-life of quinine in the elderly group (18.4 +/- 5.7 [standard deviation] h vs 10.5 +/- 1.6 h, P less than 0.05). There was no significant difference in the renal clearance of quinine between the young and the elderly (P greater than 0.05). However, elderly subjects excreted 16.6 +/- 3.7% of the dose as unchanged quinine in the urine and this was significantly greater (P less than 0.005) than the amount excreted by the young (11.2 +/- 2.5%). The results of this study indicate that the elimination processes for quinine are impaired in normal elderly subjects. The clinical significance of these findings is unknown, but they indicate the need for caution in the administration of quinine to elderly patients.
These results suggest that there is no significant interaction between the parent compound quinine and grapefruit juice, so it is not necessary to advise patients against ingesting grapefruit juice at the same time that they take quinine. Since quinine is a low clearance drug with a relatively high oral bioavailability, and is primarily metabolised by human liver CYP3A4, the lack of effect of grapefruit juice on quinine pharmacokinetics supports the view that the site of CYP inhibition by grapefruit juice is mainly in the gut.
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