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Abstract

The pharmacokinetics of cyclosporine. I. Single dose and constant rate infusion studies in the rabbit.

W M Awni and R J Sawchuk
Drug Metabolism and Disposition March 1985, 13 (2) 127-132;
W M Awni
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R J Sawchuk
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Abstract

A two-part study was conducted to characterize the pharmacokinetics of cyclosporine in rabbits. First, cyclosporine was given iv as boluses to nine rabbits in doses of 5, 10, and 20 mg/kg. At each dose level, three rabbits were used. Analysis of blood samples collected was performed by HPLC. The data indicate an increase in the half-life of the terminal phase (255 to 550 min), and in the volume of distribution at steady state (3.16 to 7.82 liters/kg) with increasing dose (5 to 20 mg/kg). Cyclosporine was then administered to three rabbits by constant rate iv infusion. The infusion rate was altered to provide three different steady states within 36 hr in each animal. Infusion rates in two rabbits were increased from 16.8 to 65.4 micrograms/min, and in the third rabbit they were decreased from 65.4 to 16.8 micrograms/min. Blood samples were collected during and postinfusion. Doubling the infusion rate within each animal produced less than double the steady state concentration. All three rabbits showed the same trend. Thus, the total body clearance of cyclosporine increased with increasing infusion rate, indicating nonlinear pharmacokinetic behavior of cyclosporine in rabbits.

 

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Drug Metabolism and Disposition
Vol. 13, Issue 2
1 Mar 1985
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Abstract

The pharmacokinetics of cyclosporine. I. Single dose and constant rate infusion studies in the rabbit.

W M Awni and R J Sawchuk
Drug Metabolism and Disposition March 1, 1985, 13 (2) 127-132;

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Abstract

The pharmacokinetics of cyclosporine. I. Single dose and constant rate infusion studies in the rabbit.

W M Awni and R J Sawchuk
Drug Metabolism and Disposition March 1, 1985, 13 (2) 127-132;
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