Related Experiment Video
Updated: May 25, 2026
04:41
Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas
Published on: July 25, 2025
S-ketamine concentrations are greatly increased by grapefruit juice
Marko A Peltoniemi1, Teijo I Saari, Nora M Hagelberg
1Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, Kiinamyllynkatu 4-8, Turku, Finland.
European Journal of Clinical Pharmacology
|January 31, 2012
Summary
Grapefruit juice significantly increases oral S-ketamine plasma concentrations and half-life in healthy volunteers. Consider reducing S-ketamine dosage when taken with grapefruit juice.
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacokinetics
Background:
- Oral S-ketamine is used for its therapeutic effects.
- Grapefruit juice is known to interact with various medications.
- Understanding these interactions is crucial for patient safety.
Purpose of the Study:
- To investigate the pharmacokinetic and pharmacodynamic effects of grapefruit juice on oral S-ketamine.
- To determine if grapefruit juice alters S-ketamine metabolism and efficacy.
Main Methods:
- A randomized crossover study in 12 healthy volunteers.
- Participants consumed grapefruit juice or water for 5 days.
- Oral S-ketamine was administered on day 5, with pharmacokinetic and pharmacodynamic variables measured.
Main Results:
- Grapefruit juice increased S-ketamine area under the curve (AUC) by 3.0-fold and Cmax by 2.1-fold.
- Elimination half-life increased by 24%, and the metabolite-to-drug ratio decreased by 57%.
- Self-rated relaxation decreased, while cognitive performance improved; other effects were unchanged.
Conclusions:
- Grapefruit juice significantly elevates oral S-ketamine plasma concentrations in healthy individuals.
- Concomitant use of grapefruit juice with oral S-ketamine may necessitate dose adjustments.
Related Concept Videos
01:26Pharmacokinetics: Drug–Food and Drug–Viral Interactions
A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of many...
01:25Pharmacokinetics: Drug–Drug Interactions
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
01:17Sedatives and Hypnotics Drugs: Miscellaneous Agents
Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...