Influence of honey on orally and intravenously administered diltiazem kinetics in rabbits

Effect of honey on plasma concentration of diltiazem after oral and intravenous administration in rabbits, has been studied. For oral study, single dose of diltiazem (5 mg/kg, p.o.) along with saline was administered to New Zealand white rabbits (n=8). Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hr after drug administration from marginal ear vein. After a washout period of one week, diltiazem was administered with honey (2.34 ml/kg; p.o.) and the blood samples were collected as above. To the same animals honey (2.34 ml/kg; p.o.) was continued once daily for 7 days. On 8th day, honey and diltiazem were administered simultaneously and blood samples were collected at similar time intervals as mentioned above. For intravenous study the pharmacokinetic was done in each animal on two occasions. The first study was done after single dose administration of diltiazem (5 mg/kg; i.v.) along with saline (2.34 ml/kg; p.o.). Blood samples were collected at 0, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4 and 6 hr after i.v. diltiazem administration. The same animals were treated with honey (2.34 ml/kg; p.o.) for seven days. On day 8, the second study was carried out with single dose i.v. administration of diltiazem along with honey (2.34 ml/kg; p.o.) and blood samples were collected. In the oral study, single dose administration of honey decreased the AUC and Cmax of diltiazem associated with significant increase in clearance and volume of distribution when compared to saline treated group. After one week administration of honey, diltiazem kinetic data showed further reduction in AUC and Cmax and increase in clearance and volume of distribution. In the i.v. study also, multiple dose administration of honey significantly reduced the AUC and increased the clearance value of diltiazem. The results suggest that honey may decrease the plasma concentration of diltiazem after its oral or i.v. administration in rabbits.