title: Effects of Thymoquinone on the Pharmacokinetics and Pharmacodynamics of Glibenclamide in a Rat Model.
abstract: Glibenclamide and thymoquinone plasma concentrations were analysed using a sensitive RP-HPLC method, and non-compartmental model pharmacokinetic parameters were calculated. The maximum reduction in blood glucose level was observed 3 hours following glibenclamide administration, which reached 47.4% of baseline, whereas it was reduced by 53.0% to 56.2% when co-administrated with thymoquinone. Plasma concentration of glibenclamide was increased by 13.4% and 21.8% by the co-administration of thymoquinone as single and multiple doses, respectively (P<0.05). The AUC and TI/2 of glibenclamide were also increased respectively by 32.0% and 17.4% with a thymoquinone single dose, and by 52.5% and 92.8% after chronic treatment. Furthermore, diabetic rats treated with thymoquinone demonstrated a marked decrease in hepatic protein expressions of CYP3A2 and CYP2C 11 enzymes that are responsible for the metabolism of glibenclamide. The current data suggest that thymoquinone exhibits a synergistic effect with glibenclamide on glucose level, which could be explained by reducing CYP450 activity at the protein level.
authors.forename: Ajaz
authors.initials: A
authors.lastname: Ahmad
authors.forename: Rao Muzaffar A
authors.initials: RM
authors.lastname: Khan
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Alkharfy
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.forename: Fahad I
authors.initials: FI
authors.lastname: Al-Jenoobi
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al-Mohizea
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D016227:Benzoquinones / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D005905:Glyburide / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D031844:Nigella / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; C003466:thymoquinone; D005905:Glyburide