Okonta JM, Uboh M, Obonga WO. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit. Indian Journal of Pharmaceutical Sciences. 2008;70(2):230-232. doi:10.4103/0250-474X.41462.
<snip from full text>Abstract
The effect of ginger on the pharmacokinectic of metronidazole was studied using rabbits in a crossover study method. The relevance of this study borders on the wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole that is commonly used for every gastrointestinal complain in our communities without prescription. Ginger significantly increased the absorption and plasma half-life, and significantly decreased the elimination rate constant and clearance of metronidazole (P<0.05). Thus, in clinical practice, the patients should be advised on the serious implication of using both items together.
The observations from our data showed that ginger, as a spice, condiment and phytotherapeutic agent, has definite and significant effects on the absorption kinetics of metronidazole. Since the peak plasma concentration of metronidazole when co administered with ginger occurred at about two hours later than that of metronidazole alone, its an indication that ginger may have caused delay in the rate of absorption of oral metronidazole but enhanced the extent of absorption considering the significant difference between the AUC0-24h of metronidazole alone and metronidazole plus ginger group. Ginger is known to improve blood circulation and bioavailability of some herbs5,12 when concurrently administered or co-formulated. It has also been reported to have spasmolytic effect and do cause smooth muscles relaxation6. These effects may have caused a reduction in gastric emptying, gastrointestinal motility and increased the blood circulation to the gastrointestinal tract thereby facilitating the increased absorption of metronidazole.
The elimination rate constant (kel) and clearance of a drug indicates the proportion of that drug that is removed from the body14 and half-life is a reciprocal function of these. As the co administration of ginger and metronidazole reduced the elimination rate constant and the clearance of the drug especially in linear kinetic, it invariably caused prolongation of the half-life. The liver is the main site of metabolism of metronidazole and about 50% of the drug is cleared from the systemic circulation by the liver9; since ginger decreased the clearance of the drug, it may be that ginger altered the metabolism of the drug by the liver.
These pharmacokinectic effects of ginger must be cautiously considered if the metronidazole must be used by a patient that consumes ginger in whatever form as the peak plasma concentrations of approximately 5 to 10 μg/ml are achieved within 1-3 hours after single doses of 250 and 500 mg of oral metronidazole13, and the co administration of ginger and metronidazole at 3 mg/kg increased the peak plasma concentration from 4.23 to 16.50 μg/ml, which is about four folds.
In conclusion, this study revealed that ginger could cause increase in the bioavailability and half-life, and decrease in the clearance and elimination rate constant of metronidazole per oral. This may pose a negative implication in clinical practice as toxicity of metronidazole may easily be reached especially during multiple dosing because of the possibility of drug accumulation.