Effects of SMS 201-995 on the pharmacokinetic profile and cellular immune and toxic effects of cyclosporine in male Wistar rats.
The immunosuppressant cyclosporine and the long-acting somatostatin analog SMS 201-995 (octreotide acetate) may have to be given simultaneously in diseases such as pancreatic transplantation. The aim of the study was to evaluate the effects of SMS 201-995 on the pharmacokinetics of cyclosporine, and to assess whether the addition of SMS 201-995 altered some of the cellular immune and toxic (renal, hepatic, glucose tolerance) effects of cyclosporine. Male Wistar rats were treated with cyclosporine 10 mg/kg/day, SMS 201-995 100 micrograms/kg b.i.d., a combination of the two drugs, or the vehicle alone. The addition of SMS 201-995 delayed the peak plasma levels of cyclosporine without affecting the through levels, and did not alter the effects of cyclosporine on the mononuclear cell subsets. This combination caused significant increases in plasma creatinine and hepatic enzymes, suggesting renal and hepatic toxicity, and severe glucose intolerance. If present in humans, the appearance of severe glucose intolerance with combined administration of SMS 201-995 and cyclosporine for pancreatic transplantation could be misinterpreted as rejection and lead to inappropriate interventions.
Yale
J F
JF
McGill Nutrition and Food Science Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.
Ahmed
S
S
Maharajh
G
G
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003524:Cyclosporins / Q000493:pharmacokinetics* / Q000633:toxicity; D004347:Drug Interactions; D007111:Immunity, Cellular / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D003524:Cyclosporins; D007328:Insulin; D015282:Octreotide