Pharmacokinetic changes of diltiazem and desacetyldiltiazem after oral administration of diltiazem in rabbits with diabetes mellitus induced by alloxan.
Physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of drugs used to treat hypertension resulting from diabetic complications. Hence, the pharmacokinetics of diltiazem (DTZ) and its metabolite, desacetyldiltiazem (DAD), were investigated after oral administration of DTZ. DTZ, 20 mg/kg, was orally administered to control rabbits and rabbits with fifth day (experiment was performed at fifth day after first and second days intravenous administration of alloxan) and 13th day (experiment was performed at 13th day after first, second, sixth, and 10th days intravenous administration of alloxan) diabetes mellitus induced by alloxan. Impaired kidney and liver functions were observed in both diabetic groups based on plasma chemistry data and/or tissue microscopy. After oral administration of DTZ, the area under the plasma concentration-time curve from time zero to time infinity were 767, 1280 and 1550 ng h/ml for control rabbits and fifth and 13th days diabetes mellitus rabbits, respectively. The values in diabetes mellitus rabbits were significantly different as compared to control rabbits. The terminal half-lives of DTZ were significantly longer in fifth (13.4 h) and 13th (13.0 h) days diabetes mellitus rabbits than that in control rabbits (8.76 h). The renal clearances of DTZ in fifth (0.3161/h/kg) and 13th (0.2641/h/kg) days diabetes mellitus rabbits were significantly slower than that in control rabbits (0.5051/h/kg), and this could be due to impaired kidney function in the diabetes mellitus rabbits. However, other pharmacokinetic parameters of DAD were not significantly different among three groups of rabbits.
Choi
Jun S
JS
College of Pharmacy, Chosun University, Dong-Gu, Kwangju, Republic of Korea. jsachoi@mail.chosun.ac.kr
Kim
Yoon G
YG
D000284:Administration, Oral; D000496:Alloxan; D000818:Animals; D019540:Area Under Curve; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D051381:Rats
D000496:Alloxan; C037769:deacetyldiltiazem; D004110:Diltiazem