Isoflurane alters the kinetics of oral cyclosporine.
Cyclosporine is an important immunosuppressive agent often given orally preoperatively to patients undergoing organ transplantation. The aim of the present study was to evaluate the effects of anesthesia on the pharmacokinetics of orally administered cyclosporine. Sixty unanesthetized fasting female Lewis rats were given 25 mg/kg cyclosporine by gastric tube and were then randomized to immediately receive an isoflurane anesthetic (n = 30) or to serve as nonanesthetized controls. At 1, 2, 3, 4, and 6 h after the administration of the cyclosporine, six animals from each group (while still anesthetized for those in the anesthesia group) were killed, and arterial blood and the entire bowel from the esophagogastric junction to the ileocecal junction were removed for measurement of cyclosporine concentrations. A subsequent study with six animals in each group was performed to examine more closely the distribution of cyclosporine in the stomach and small intestine 4 h after the oral dose. In these animals the cyclosporine concentration in the stomach and in five 10-cm-long segments of small bowel was assayed. In all studies of gastrointestinal specimens, the cyclosporine extracted is a combination of that contained in the lumen and the wall. At all times except at 6 h, the blood cyclosporine levels were significantly higher in the control group than in the isoflurane group. Conversely, the amount of cyclosporine in the distal small bowel of control rats was increased as compared with the anesthetized animals. In the animals studied at 4 h, the amount of cyclosporine in the stomach of control rats was significantly lower than that in the anesthetized animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Gelb
A W
AW
Department of Anaesthesia, University Hospital, London, Ontario, Canada.
Freeman
D
D
Robertson
K M
KM
Zhang
C
C
D000284:Administration, Oral; D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D007530:Isoflurane / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
D003524:Cyclosporins; D007530:Isoflurane