Effect of honey on CYP3A4, CYP2D6 and CYP2C19 enzyme activity in healthy human volunteers.

Honey is a common food supplement but not many studies have studied honey and drug interaction. This study investigates the influence of 7 days of honey administration on the activity of CYP3A4, CYP2D6 and CYP2C19 drug-metabolizing enzymes in healthy volunteers by using appropriate biomarker and probe drugs. A within-group pharmacokinetic study was done in 12 healthy volunteers. Urine samples (0-8 hr) were collected after administration of 30 mg of oral dextromethorphan (probe drug for CYP2D6) for analysis of dextromethorphan and dextrorphan. A plasma sample (4 hr) was collected after administration of 200 mg of oral proguanil (probe drug for CYP2C19) for the analysis of proguanil and cycloguanil. Urine samples (0-24 hr) were collected for the analysis of 6beta-hydroxycortisol (biomarker for CYP3A4). The volunteers were administered honey for 7 days. Subsequently blood and urine samples were collected after drug dosing as before. These samples were analysed for drug and metabolite concentrations in urine and plasma using high performance liquid chromatography method. Seven days of honey administration resulted in statistically significant increase in 24-hr urinary excretion of 6beta-hydroxycortisol. However, the metabolic ratios of dextromethorphan and proguanil were not significantly altered after 7 days of honey administration. Honey obtained from Western Ghats of southern India may induce CYP3A4 enzyme activity but not CYP2D6 and CYP2C19 enzyme activities.

Opioid mediated anti-nociceptive effect of domperidone and cisapride in mice.

AIM: To study the anti-nociceptive effect of domperidone and cisapride in mice. METHODS: Initially, the effect of these drugs on motor activity was tested using rotarod. The anti-nociception was tested using chemical and mechanical assay. In the chemical assay, the number of abdominal constrictions either in the saline treated animals or in the domperidone/cisapride (1, 5, or 10 mg/kg either po or ip) treated mice, were recorded for a period of 30 min after acetic acid challenge (10 mL/kg, of 0.6 % acetic acid ip). In the tail clip assay, the time taken by the mouse to make attempts to dislodge the bulldog clamp placed at the tail (reaction time) was recorded with a cut off time of 30 s. The role of opioid pathways was examined by pretreating the animals with naloxone (1 mg/kg, ip) 30 min prior to domperidone and cisapride. RESULTS: Domperidone and cisapride, both reduced the number of abdominal constrictions when given orally or intraperitoneally. Domperidone (5 mg/kg) inhibited it to the extent of 57.0 % after po and 54.6 % after ip. The inhibition after cisapride (5 mg/kg) was 65.1 % (po) and 71.6 % (ip). Naloxone pretreatment reduced this inhibition (57.0 % vs 10.3 % for domperidone and induced hyperalgesia by antagonizing the inhibition and enhanced analgesia to the extent of 28.4 % for cisapride). The reaction time was increased by domperidone (10 mg/kg, ip) from 1.6 s +/- 1.0 s to 14.8 s +/- 0.5 s and cisapride (10 mg/kg, ip) from 3.3 s +/- 1.0 s to 14.8 s +/- 0.5 s. CONCLUSION: Domperidone and cisapride exhibited a significant anti-nociceptive activity after oral as well as intraperitoneal administration. A role for opioid pathways is indicated. Since domperidone is likely to exert less extrapyramidal effects, it can be substituted for metoclopramide, which is now widely used as an analgesic either alone or as an adjuvant.