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.
Aqueous extract of Hibiscus sabdariffa lowered T better than simvastatin and enhanced the antihyperlipidaemic activity of the drug when co-administered at low doses in an animal model. However, aqueous beverage of Hibiscus sabdariffa caused a significant herb-drug interaction resulting in overall reduction in exposure to simvastatin in humans. Caution should thus be placed on clinical judgement or recommendations based on the animal results. Nevertheless, co-administration of the beverage with simvastatin should be discouraged until more clinical data are available.
HighlightsVaried disposition imparts on the tolerance and safety of quinine, and thus constitutes a major limiting consideration for its dosing in uncomplicated malaria. Utilizing a population approach, the effect of body weight and infection status on disposition parameters of quinine were evaluated in Nigerian subjects.A reversal of infection-induced changes in volume of distribution and clearance after 48 h of chronic quinine administration was noted.It is hypothesized that a downward review of quinine regimen post-48 h of chronic administration, in the event of complete parasitaemia clearance, might be a useful approach in enhancing tolerance and safety.
IntroductionThere is a scarcity of epidemiological data on neurodegenerative diseases (NDs) in East Africa. This meta-analysis provides the regional prevalence of NDs, their contributing factors, and evidence of change over time concerning gender per age or year.MethodsArticles were retrieved from electronic databases following the PRISMA standard.ResultsForty-two studies were reviewed, and 25 were meta-analyzed with a random-effects model. The pool estimate proportion of 15.27%, 95% CI (0.09–0.23) (I2 = 98.25%), (Q = 1,369.15, p < 0.0001) among a population of 15,813 male/female and 1,257 with NDs. Epidemiological characteristics associated with NDs include Dyskinesias prevalence 55.4%, 95% CI (13.5; 90.9), I2 (96%) and subsistence farming prevalence 11.3%, 95% CI (5.8; 20.9), I2 (99%). Publication bias by Egger test was (z = 4.1913, p < 0.0001), while rank correlation test using Kendall's model was (tau = 0.1237, p = 0.3873). Heterogeneity (R2 design = 5.23%, p design < 0.0001; R2 size = 52.163%, p size < 0.001; and R2 period = 48.13, p period < 0.0001. Covariates (R2 design + size + period = 48.41%, p < 0.001).ConclusionThere is a high prevalence of NDs in the East African region, which could impact life expectancy, morbidity, and quality of life. Thus, early screening and regular surveillance could assist in management strategies.
The literature abounds with reports on the utilization of herbal medications for the treatment of diabetes mellitus since time immemorial, but very few of these herbal products have undergone clinical trials. Also, studies on the herb-drug interactions were limited. Due to the complex phytochemical composition of the herbs, concomitant administration with conventional drugs resulted in alterations of pharmacological effects of some drugs. Evidences of beneficial interactions were identified for medical exploitation.
Aim of the Study: Conventional antimalarial drugs are used concurrently with herbal remedies in malarial endemic developing countries. Vernonia amygdalina is one of such popular herbs used in the treatment of malaria. This study aimed at investigating the antimalarial chemotherapeutic interaction of Vernonia amygdalina (VA) when combined with Amodiaquine (AQ) and/or Artesunate (AS) in a murine Plasmodium berghei malaria model. Methodology: Various doses of aqueous VA leaf extract (100-500 mg/kg/day), AQ (2-10 mg/kg/day) and AS (0.8-4 mg/kg/day) were administered orally to P berghei.-infected Swiss albino mice to determine their sub-therapeutic doses. These doses were subsequently used to investigate the chemotherapeutic interactions of VA with AQ and/or AS in both early and established malaria infection test models. The survival of animals with established infections that received different drug/herb treatments were determined using their mean survival time (days) and Kaplan-Meier survival curves (percentage). Using GraphPad Instat (version 3.10) and PrismR (version 5.01) the data obtained were subjected to One-way ANOVA, followed by Student-Newman-Keuls test. P < .05 was considered statistically significant. Results: The sub-therapeutic doses of VA, AQ and AS were found to be 100 mg/kg, 2 mg/kg and 2.4 mg/kg, respectively. The chemosuppressive effect of AQ or AS was significantly increased (p< 0.05) when administered in combination with the VA extract. Similarly, combination of VA extract with AQ or AS resulted in significant (P < .05) parasite clearance when compared to the effects of the herb or the conventional drugs administered separately. The mean survival period of animals with established infection was also significantly enhanced by the VA alone or with AQ (or AS) compared to placebo.
Background and objective: Malaria and tuberculosis remain endemic in tropical regions and most often coexist, increasing the burden of malaria mortality due to unintended interactions of the co-administered drugs employed in the management of the infections. Rifampicin (RIF) and amodiaquine (ADQ) are likely to be administered concurrently in the treatment of patients with tuberculosis and malaria. The metabolism of ADQ is mediated principally by CYP2C8, while RIF is a known inducer of this enzyme. This study, therefore, investigated the effect of RIF on the disposition of ADQ, a major partner drug in the first-line treatment against uncomplicated malaria in line with the World Health Organization recommendations. Methods:Sixteen healthy volunteers received oral 150 mg dose of RIF daily for 5 days with or without oral 600 mg single dose of ADQ on the fifth day (5 th dose) with a 4-week wash out period, in a crossover fashion. Blood samples were collected at predetermined time intervals of 0, 1, 2, 4, 6, 8, 12, 24, 36 and 48 h. Plasma samples were analyzed for ADQ and its major metabolite desethylamodiaquine using a validated RP-high-performance liquid chromatography. Pharmacokinetic parameters were obtained using appropriate software and subjected to appropriate statistical analysis. Results:Coadministration of ADQ and RIF resulted in significant decreases in the critical pharmacokinetic parameters of ADQ, such as area under the curve (AUC 0-∞ ) of about 66%, time to peak plasma concentration (Tmax) of about 10%, maximum plasma concentration of about 44%, and elimination half-life of about 55%, while the AUC 0-∞ and Tmax of the main metabolite desethylamodiaquine increased about 2-fold and 3-fold respectively during the coadministration of RIF with ADQ. The metabolic ratio increased significantly, from 1.55 to 2.68. The AUC 0-∞ and Tmax of the drug ADQ, as well as the maximum concentration of both the drug and its metabolite fell outside the point of estimates of the test/reference ratio of the geometric means of 80-125% of bioequivalence range. Conclusions:An interaction was established during coadministration of RIF and ADQ, confirming RIF as a strong inducer of CYP2C8 in vivo, which may lead to malaria therapeutic failure or adverse drug reactions with ADQ and contribute to the rate at which resistance to ADQ develops.
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