Pharmacokinetics of ranitidine in patients with renal failure.
The pharmacokinetics of ranitidine were studied in ten patients with renal failure (creatinine clearance, 6-54 mL/min) after intravenous (IV) (50 mg) and oral doses (150 mg). After oral administration, peak plasma concentrations of 378-808 ng/mL were obtained in two to six hours. Plasma concentrations declined very slowly and concentrations greater than 100 ng/mL were obtained for 16 to 20 hours after the dose. The elimination half-life following oral administration was 8.5 +/- 2.8 hours (standard deviation [SD]), and the bioavailability of ranitidine was 43.3% +/- 10.5%. After IV administration, the elimination half-life, plasma clearance, renal clearance, and volume of distribution were 7.0 +/- 1.0 hours, 170 +/- 38 mL/min, 36.0 +/- 25.0 mL/min, and 1.3 +/- 0.4 L/kg, respectively. About 20% of the IV dose and 9% of the oral dose were recovered unchanged in urine. There was a significant correlation between the renal clearance of ranitidine and creatinine clearance (r = .74, P less than .05) after IV administration. The elimination half-life in patients with renal insufficiency is about three times greater than that reported in the literature for healthy subjects. Similarly, the plasma clearance in these patients is about 20% of that reported in healthy subjects. The results indicate that ranitidine elimination is appreciably reduced in renal failure and that an adjustment of dose in patients with renal failure is warranted. A dose of 75 mg bid may be adequate in maintaining the therapeutic plasma concentrations that are required for adequate H2-blocking activity.
Garg
D C
DC
Baltodano
N
N
Jallad
N S
NS
Perez
G
G
Oster
J R
JR
Eshelman
F N
FN
Weidler
D J
DJ
D000368:Aged; D001682:Biological Availability; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007676:Kidney Failure, Chronic / Q000097:blood*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011899:Ranitidine / Q000097:blood*
D011899:Ranitidine; D003404:Creatinine