The impact of body weight on cyclosporine pharmacokinetics in renal transplant recipients.
In order to assess the effect of body weight on cyclosporine disposition, 45 adult uremic candidates for renal transplantation underwent detailed nutritional assessment and pharmacokinetic analysis. There were 10 obese and 35 nonobese patients defined as actual body weight (ABW) greater than 125 Per cent of ideal body weight (IBW), and arm fat area greater than 90th percentile. There was no significant difference in demographic variables such as age, sex, number of diabetics, IBW, serum lipids, or liver function tests between the 2 groups. Although there was a significant difference in ABW, pharmacokinetic analyses failed to demonstrate significant differences in bioavailability, elimination half-life, clearance, or apparent steady state volume of distribution when these calculations were normalized by IBW, body surface area, or as absolute values. Multiple stepwise linear regression failed to demonstrate a significant correlation between serum lipids or body size measurements and these parameters. When dosed according to ABW, obese recipients of renal allografts had a mean serum RIA trough level of 227 ng/ml as compared to 121 ng/ml in nonobese recipients on day 7. Therefore in order to achieve comparable drug concentrations in the early transplant period, CsA should be given to obese patients based on their IBW.
Flechner
S M
SM
Department of Surgery, Stanford University School of Medicine, California 94305.
Kolbeinsson
M E
ME
Tam
J
J
Lum
B
B
D000328:Adult; D001835:Body Weight; D003524:Cyclosporins / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D003524:Cyclosporins