Pharmacokinetic changes of acebutolol after oral administration in rabbits with diabetes mellitus induced by alloxan.
Because physiological changes that potentially alter pharmacokinetics occurs in diabetes mellitus patients, pharamacokinetics of drugs used in the treatment of hypertension was studied using acebutolol as a model anti-hypertensive drug. Thus, the pharmacokinetics of acebutolol was investigated after oral administration of acebutolol (15 mg/kg) to control rabbits and rabbits with acute or chronic diabetes mellitus induced by alloxan. Kidney and liver functions were documented for acute and chronic diabetes mellitus groups based on plasma chemistry data. After oral administration of acebutolol to acute and chronic groups, the plasma concentrations appeared higher; As a result, area under the plasma concentration-time curve from time zero to time infinity10575 and 8668 microg x h/mL for acute and chronic group, respectively. In comparison, the area was apparently smaller in the control group (i.e., 7132 microg x h/mL). The half-life in acute groups was significantly prolonged 8.45 h compared with the half-life in the control group (i.e., 6.30 h). Alteration in acebutolol pharmacokinetics was more pronounced in the acute group as evidenced by the significantly higher values the area under the plasma concentration time curve, absorption rate constant and maximum plasma concentration compared with chronic or control group. Therefore, these observations indicate that acebutolol pharmacokinetics may be affected in patients with diabetes mellitus, especially in the early stage of the disease.
Choi
Dong Hyun
DH
College of Medicine, Chosun University, Kwangju 501-759, Korea.
Bae
Hak Yeon
HY
Choi
Jun Shik
JS
D000070:Acebutolol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000188:drug therapy*; D011817:Rabbits
D000070:Acebutolol