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Effect of cimetidine on pharmacokinetics of orally administered cyclosporine in healthy dogs

Jenise Coyne DaigleDepartment of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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 DVM
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Giselle HosgoodDepartment of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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 BVSc, MS
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Carol S. FoilDepartment of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

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Robert P. HunterDepartment of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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 PhD

Abstract

Objective—To describe the pharmacokinetics of cyclosporine (CyA) in healthy dogs after oral administration alone or in combination with orally administered cimetidine.

Animals—10 healthy adult Beagles.

Procedure—Dogs were randomly assigned to receive CyA alone or CyA in combination with cimetidine. After a washout period of 2 weeks, dogs then received the alternate treatment. The CyA plus cimetidine treatment required administration of cimetidine (15 mg/kg of body weight, PO, q 8 h) for 8 days and administration of CyA (5 mg/kg, PO, q 24 h) on days 6 through 8. The CyA treatment alone required administration of CyA (5 mg/kg, PO, q 24 h) for 3 days. On the third day of CyA administration during each treatment, blood samples were collected immediately before (time 0) and 0.5, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 11, 13, 15, 21, and 24 hours after initiating CyA administration.

Results—Time until maximum CyA concentration was significantly longer for CyA in combination with cimetidine. Assessment of estimated pharmacokinetic variables revealed a significantly faster rate of change in the distribution phase for CyA in combination with cimetidine. Maximum CyA concentration differed significantly among dogs but did not differ significantly between treatments.

Conclusions and Clinical Relevance—Analysis of our data suggests that cimetidine may affect absorption of orally administered CyA, but overall, it does not affect the pharmacokinetics of CyA. There is considerable variability in the maximum concentration of CyA among dogs, and monitoring of blood concentrations of CyA during treatment is advised. (Am J Vet Res 2001;62:1046–1050)

Abstract

Objective—To describe the pharmacokinetics of cyclosporine (CyA) in healthy dogs after oral administration alone or in combination with orally administered cimetidine.

Animals—10 healthy adult Beagles.

Procedure—Dogs were randomly assigned to receive CyA alone or CyA in combination with cimetidine. After a washout period of 2 weeks, dogs then received the alternate treatment. The CyA plus cimetidine treatment required administration of cimetidine (15 mg/kg of body weight, PO, q 8 h) for 8 days and administration of CyA (5 mg/kg, PO, q 24 h) on days 6 through 8. The CyA treatment alone required administration of CyA (5 mg/kg, PO, q 24 h) for 3 days. On the third day of CyA administration during each treatment, blood samples were collected immediately before (time 0) and 0.5, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 11, 13, 15, 21, and 24 hours after initiating CyA administration.

Results—Time until maximum CyA concentration was significantly longer for CyA in combination with cimetidine. Assessment of estimated pharmacokinetic variables revealed a significantly faster rate of change in the distribution phase for CyA in combination with cimetidine. Maximum CyA concentration differed significantly among dogs but did not differ significantly between treatments.

Conclusions and Clinical Relevance—Analysis of our data suggests that cimetidine may affect absorption of orally administered CyA, but overall, it does not affect the pharmacokinetics of CyA. There is considerable variability in the maximum concentration of CyA among dogs, and monitoring of blood concentrations of CyA during treatment is advised. (Am J Vet Res 2001;62:1046–1050)