Effect of dehusked Garcinia kola seeds on the overall pharmacokinetics of quinine in healthy Nigerian volunteers

Abstract

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.

Modulation of cytochrome P450 3A4 mediated quinine metabolism in healthy volunteers by two honey samples from different floral and geographical sources

“…18 Contrary to the result of honey sample from Northern Nigeria, a very recent quinine-honey interaction study of Nigeria honey sample from western region of Nigeria indicated a non-significant dose dependent biphasic effect on quinine metabolism with a lower dose of honey suggesting stimulation and a higher dose indicative of inhibition in CYP3A4 activity in the same group of healthy volunteers. 19 Furthermore, six out of the eight subjects (group A) who used Northern honey showed increased enzyme activity as reflected by a higher metabolic ratio post honey intake ( Figure 1). In group B (used eastern honey); stimulatory and inhibitory activity on CYP3A4 was comparatively spread among the volunteers.…”

“…The calibration procedures were as previously reported. 19 The limit of quantitation was 0.37 µg/ml and 0.5 µg/ml for quinine and 3-hydroxyquinine, respectively. At concentrations of 0.25 and 4.0 µg/ml, the intra-day and inter-day coefficient of variation was not greater than 4 % for both quinine and 3-hydroxyquinine.…”

“…19,29 The Agilent HPLC machine (Agilent 1200 series, Agilent Technologies, Santa Clara, California) used in the analysis was fitted with an isocratic pump (model G1341A) coupled with variable wavelength detector [Agilent Technologies; standard version (model G1341B)] set at 254 nm. Drug and metabolite extraction from 1ml of plasma (to which had been added 3.0 µg/ml of primaquine as internal standard) was achieved by precipitating with 200 µl of perchloric acid (70% w/w) and alkalinisation with NaOH, followed by extraction with diethylether and subsequent back-extraction into 0.1 M HCl.…”

“…[14][15][16][17] However two studies in man have found no significant modulating effect of a German and a Nigeria honey on CYP3A4 activity in humans. 18,19 There is a resurgence of the use of quinine in the treatment of malaria because of resistance development to the other amino quinolones. 20 There are numerous evidences that suggest metabolism of quinine to 3-hydroxyquinine is mediated by CYP3A4 and may be used for phenotying CYP3A4 activity.…”

“…27 The only available drughoney interaction study of honey from Africa by Igbinoba et al suggested that honey sample from western region of Nigeria did not significantly alter CYP3A-mediated metabolism of quinine in healthy human volunteers though a dose-dependent biphasic effect on the pattern of quinine metabolism was observed. 19 Indeed Nigeria is a very large country with different climatic condition and vegetation along the different region and geographical spread. Knowing that numerous factors such as climate and floral sources may affect the honey constituents with attendant variation in honey, it was deemed necessary to study samples of honey from other geographical region within Nigeria to know how it will modulate CYP3A4 metabolism of quinine.…”