Ginger significantly decreased the oral bioavailability of cyclosporine in rats.
Ginger (roots of Zingiber officinale ROSCOE) is a popular spice and herbal medicine worldwide. Cyclosporine is clinically used as an important immunosupressant with narrow therapeutic index. This study attempted to investigate the effect of ginger juice on the pharmacokinetics of cyclosporine in rats. Rats were orally administered cyclosporine alone and in combination with ginger juice (5 ml/kg) concomitantly, as well as 2 hours after the ginger juice, respectively, in crossover designs. In addition, rats were intravenously administered cyclosporine with and without an oral dose of ginger juice (5 ml/kg). The blood samples were withdrawn via cardiopuncture at determined time points and cyclosporine concentrations were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters of cyclosporine were calculated using a non-compartment model of WINNONLIN. The results indicated that concomitant intake of ginger significantly decreased C(max) and AUC(0-t) of oral cyclosporine by 70.9% and 63.1%, respectively. The intake of ginger 2 hours before cyclosporine significantly decreased C(max) and AUC(0-t) by 51.4% and 40.3%, respectively. In contrast, the pharmacokinetics of intravenous cyclosporine not altered by orally in combination with ginger juice. In conclusion, ginger significantly decreased the oral bioavailability of cyclosporine, and the interaction should occur at the absorption phase. Patients treated with cyclosporine should be discouraged from using ginger products to ensure the efficacy of cyclosporine.
Chiang
Hsiu-Mei
HM
School of Cosmeceutics, China Medical University, Taichung, Taiwan, 404, ROC.
Chao
Pei-Dawn Lee
PD
Hsiu
Su-Lan
SL
Wen
Kuo-Ching
KC
Tsai
Shang-Yuan
SY
Hou
Yu-Chi
YC
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D020939:Zingiber officinale / Q000737:chemistry*; D007082:Ileum / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020112:Rhodamine 123 / Q000378:metabolism / Q000493:pharmacokinetics
D007166:Immunosuppressive Agents; D010936:Plant Extracts; D020112:Rhodamine 123; D016572:Cyclosporine