Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function.
Pamidronate is a second-generation bisphosphonate that undergoes negligible biodegradation and is eliminated exclusively by renal excretions. Nineteen cancer patients were stratified according to baseline creatinine clearance (Clcr): group I, Clcr > 90 mL/min (n = 6); group II, Clcr 61 mL/min to 90 mL/min (n = 6); group III, Clcr 30 mL/min to 60 mL/min (n = 3); group IV, Clcr < 30 mL/min (n = 4). All patients received a single, 90-mg dose of pamidronate disodium administered in a 4-hour intravenous infusion. Plasma and urine samples were collected at intervals up to 36 and 120 hours, respectively, after the start of infusion and were assayed for pamidronate, using validated high-performance liquid chromatography. Pamidronate's pharmacokinetics were characterized by a short distribution phase (2-3 hours) followed by rapid elimination of the drug in urine. Elimination of pamidronate was slower in patients in group IV with a mean +/- standard deviation area under the plasma concentration-time curve (AUC0-36) of 19.0 +/- 4.60 micrograms.hr/mL compared with 8.1 +/- 3.13 micrograms.hr/mL in patients in group I. A linear relationship in Clcr was observed for AUC0-36 (r = 0.67), urinary excretion (r = 0.69), and renal clearance (r = 0.81). Renal clearance was proportional to Clcr for patients in all four renal-function groups. In the treatment of bone metastases of malignancy, successive doses of pamidronate are generally separated by weeks; thus, plasma accumulation in patients with renal impairment is not expected to be clinically relevant. A reduction in dose of pamidronate disodium should not be necessary in cancer patients with renal impairment.
Berenson
J R
JR
West Los Angeles Veterans Affairs Medical Center, CA, USA.
Rosen
L
L
Vescio
R
R
Lau
H S
HS
Woo
M
M
Sioufi
A
A
Kowalski
M O
MO
Knight
R D
RD
Seaman
J J
JJ
D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D004164:Diphosphonates / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D000077268:Pamidronate; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*
D004164:Diphosphonates; D000077268:Pamidronate