Pharmacokinetics of single-dose rosiglitazone in chronic ambulatory peritoneal dialysis patients

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Abstract

Background

End-stage renal disease (ESRD) is associated with marked alterations in the pharmacokinetics of many drugs, not only from reduction in renal clearance but also from changes in metabolic activity, bioavailability, volume of distribution and plasma protein binding.

Objective

To study the pharmacokinetics of a single 8-mg oral dose of rosiglitazone in patients with ESRD and requiring long-term chronic ambulatory peritoneal dialysis (CAPD).

Method

The medication was administered just before the first exchange of peritoneal dialysis fluid on the day that blood and peritoneal dialysate collection was performed.

Results

In our CAPD patients the mean (±SD) Tmax and T1/2 of rosiglitazone were 1·20 ± 0·26 and 21·38 ± 21·96 h respectively. These values were different to those reported for healthy volunteers reported in previous studies. The mean area under the concentration–time curve (AUC(0–∞)) and an average maximum observed plasma concentration (Cmax) of rosiglitazone in our CAPD patients were 4203·56 ± 2916·97 ng h/mL and 409·67 ± 148·89 ng/mL respectively. These appear no different from those reported in healthy volunteers.

Conclusion

The apparently significant difference in T1/2 of rosiglitazone in CAPD patients compared with healthy volunteers suggest that dose adjustment may be necessary in order to avoid toxicity.

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