Abstract
There is a renewed interest in thalidomide for use in malignancies and systemic inflammatory diseases. Reduced renal function is not uncommon among patients with these disease states but the pharmacokinetics has not been fully investigated. The aim of this study was to investigate the pharmacokinetics of thalidomide in haemodialysis patients while on and off dialysis and in myeloma patients with varying degrees of renal function. Two studies were performed. To establish the pharmacokinetics of thalidomide in patients with mild to moderate renal failure, blood samples were taken over 12 weeks from 40 patients with multiple myeloma. A second study was performed in six patients with end-stage renal disease both on a non-dialysis day and before and during a haemodialysis session. Thalidomide concentration was determined by HPLC. A one-compartment open model with first-order absorption and elimination was used to fit total thalidomide concentration to population pharmacokinetics and statistical models using the NONMEM program. Clearance and volumes were slightly below 10 Lh-1 and 1 L kg-1, respectively, in both patient groups. The inter- and intra-patient variability was low. Clearance was doubled during dialysis. There was no correlation between thalidomide clearance and renal function. In conclusion, the pharmacokinetics of thalidomide in patients with renal failure are very similar to values reported by others for patients with normal renal function. Although clearance during dialysis is doubled, thalidomide dose need not be changed for patients with decreased kidney function. There is also no need for a supplementary dose due to haemodialysis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1701-1706 |
| Number of pages | 6 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 55 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2003 |
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ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
Cite this
Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis. / Eriksson, Tommy; Höglund, P.; Turesson, I.; Waage, A.; Don, Burl R; Vu, J.; Scheffler, M.; Kaysen, George.
In: Journal of Pharmacy and Pharmacology, Vol. 55, No. 12, 12.2003, p. 1701-1706.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis
AU - Eriksson, Tommy
AU - Höglund, P.
AU - Turesson, I.
AU - Waage, A.
AU - Don, Burl R
AU - Vu, J.
AU - Scheffler, M.
AU - Kaysen, George
PY - 2003/12
Y1 - 2003/12
N2 - There is a renewed interest in thalidomide for use in malignancies and systemic inflammatory diseases. Reduced renal function is not uncommon among patients with these disease states but the pharmacokinetics has not been fully investigated. The aim of this study was to investigate the pharmacokinetics of thalidomide in haemodialysis patients while on and off dialysis and in myeloma patients with varying degrees of renal function. Two studies were performed. To establish the pharmacokinetics of thalidomide in patients with mild to moderate renal failure, blood samples were taken over 12 weeks from 40 patients with multiple myeloma. A second study was performed in six patients with end-stage renal disease both on a non-dialysis day and before and during a haemodialysis session. Thalidomide concentration was determined by HPLC. A one-compartment open model with first-order absorption and elimination was used to fit total thalidomide concentration to population pharmacokinetics and statistical models using the NONMEM program. Clearance and volumes were slightly below 10 Lh-1 and 1 L kg-1, respectively, in both patient groups. The inter- and intra-patient variability was low. Clearance was doubled during dialysis. There was no correlation between thalidomide clearance and renal function. In conclusion, the pharmacokinetics of thalidomide in patients with renal failure are very similar to values reported by others for patients with normal renal function. Although clearance during dialysis is doubled, thalidomide dose need not be changed for patients with decreased kidney function. There is also no need for a supplementary dose due to haemodialysis.
AB - There is a renewed interest in thalidomide for use in malignancies and systemic inflammatory diseases. Reduced renal function is not uncommon among patients with these disease states but the pharmacokinetics has not been fully investigated. The aim of this study was to investigate the pharmacokinetics of thalidomide in haemodialysis patients while on and off dialysis and in myeloma patients with varying degrees of renal function. Two studies were performed. To establish the pharmacokinetics of thalidomide in patients with mild to moderate renal failure, blood samples were taken over 12 weeks from 40 patients with multiple myeloma. A second study was performed in six patients with end-stage renal disease both on a non-dialysis day and before and during a haemodialysis session. Thalidomide concentration was determined by HPLC. A one-compartment open model with first-order absorption and elimination was used to fit total thalidomide concentration to population pharmacokinetics and statistical models using the NONMEM program. Clearance and volumes were slightly below 10 Lh-1 and 1 L kg-1, respectively, in both patient groups. The inter- and intra-patient variability was low. Clearance was doubled during dialysis. There was no correlation between thalidomide clearance and renal function. In conclusion, the pharmacokinetics of thalidomide in patients with renal failure are very similar to values reported by others for patients with normal renal function. Although clearance during dialysis is doubled, thalidomide dose need not be changed for patients with decreased kidney function. There is also no need for a supplementary dose due to haemodialysis.
UR - http://www.scopus.com/inward/record.url?scp=0347989302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0347989302&partnerID=8YFLogxK
U2 - 10.1211/0022357022241
DO - 10.1211/0022357022241
M3 - Article
C2 - 14738599
AN - SCOPUS:0347989302
VL - 55
SP - 1701
EP - 1706
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 12
ER -