The analgesic effect of ketamine is primarily based on the antagonism of the N-methyl-d-aspartate (NMDA) receptor. Activation of NMDA receptors may play a crucial role in the pathogenesis of chronic pain. Little formal research has been performed on the efficacy and safety of ketamine in chronic pain, especially concerning long-term oral administration. This review provides an overview of the available clinical data on the use of oral ketamine in chronic pain management. A literature search was performed in MEDLINE, EMBASE and the Cochrane Library, resulting in 22 relevant articles. Because most retrieved articles were of a descriptive nature (e.g. case reports and case series) a quantitative analysis was not possible. There was no consistent dose-response relation. A recommended starting dosage in ketamine-naive patients is 0.5 mg/kg racemic ketamine or 0.25 mg/kg S-ketamine as a single oral dose. The dosage is increased by the same amount if required. For a continuous analgesic effect it is usually given 3-4 times daily. The injection fluid can be taken orally. When parenteral ketamine is switched to oral administration the daily dosage can be kept equal and, depending on clinical effect and/or adverse effects, is slowly increased. The pharmacologically active metabolite norketamine is believed to contribute to the analgesic effect of oral ketamine. Lack of evidence regarding efficacy, and the poor safety profile, do not support routine use of oral ketamine in chronic pain management. Oral ketamine may have a limited place as add-on therapy in complex chronic pain patients if other therapeutic options have failed.
dMedicinal herbs may cause clinically relevant drug interactions with antiretroviral agents. Ginkgo biloba extract is a popular herbal product among HIV-infected patients because of its positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor, is increasingly being used as part of combined antiretroviral therapy. Clinical data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of raltegravir in an openlabel, randomized, two-period, crossover phase I trial in 18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of ginkgo biloba twice daily for 15 days plus a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of raltegravir on day 36 or the test and reference treatments in reverse order. Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on an empty stomach. All subjects (9 male) completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from dosing to infinity (AUC 0-ؕ ) and the maximum plasma concentration (C max ) of raltegravir with ginkgo biloba versus raltegravir alone were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The potential increase in the C max of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.