The pharmacokinetics of pravastatin in patients on chronic hemodialysis.
OBJECTIVE
The single-dose and steady-state pharmacokinetics of the HMG CoA reductase inhibitor pravastatin and its two metabolites, SQ 31,906 and SQ 31,945, were evaluated in 12 hemodialysis patients. A single 20-mg i.v. dose was employed, followed by daily oral dosing of 20 mg over four hemodialysis intervals.


RESULTS
No statistical differences in the pharmacokinetics of pravastatin or SQ 31,906 were evident when comparing the first and last days of oral dosing with pravastatin. The pharmacokinetic parameters of pravastatin and SQ 31,906 were similar to those of healthy volunteers. SQ 31,945, the inactive polar metabolite, did accumulate in dialysis patients, as evidenced by an accumulation index of 1.7 +/- 1.0. Although metabolic clearance is the predominant mode of elimination of pravastatin, hemodialysis clearances of pravastatin, SQ 31,906 and SQ 31,945 will contribute to total body clearance since dialytic clearance ranged from 40 to 80 ml.min-1.


CONCLUSIONS
Pravastatin can be safely administered in the usual dosages to subjects with renal failure on hemodialysis and no change in dosing is necessary.
Gehr
T W
TW
Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0160, USA.
Sica
D A
DA
Slugg
P H
PH
Hammett
J L
JL
Raymond
R
R
Ford
N F
NF
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D006435:Renal Dialysis
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C075237:SQ 31945; C075236:SQ 31906; D017035:Pravastatin