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Pharmacokinetics of Pamidronate Disodium in Patients with Cancer with Normal or Impaired Renal Function
Author(s) -
Berenson James R.,
Rosen Lee,
Vescio Robert,
Lau Henry S.,
Woo Margie,
Sioufi Antoine,
Kowalski M. Ortu,
Knight Robert D.,
Seaman John J.
Publication year - 1997
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1997.tb04304.x
Subject(s) - pharmacokinetics , renal function , urology , urine , medicine , urinary system , chemistry , excretion , creatinine , endocrinology
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 (Cl cr ): group I, Cl cr >90 mL/min (n = 6); group II, Cl cr 61 mL/min to 90 mL/min (n = 6); group III, Cl cr 30 mL/min to 60 mL/min (n = 3); group IV, Cl cr <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 (AUC 0–36 ) of 19.0 ± 4.60 μg·hr/mL compared with 8.1 ± 3.13 μg·hr/mL in patients in group I. A linear relationship in Cl cr was observed for AUC 0–36 (r = 0.67), urinary excretion (r = 0.69), and renal clearance (r = 0.81). Renal clearance was proportional to Cl cr 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.