Effect of urine pH on the stability of doxorubicin and its recovery from bladder instillations.
Doxorubicin (1 mg/ml) was shown to be stable when added to urine samples with a mean natural pH of 5.4 and in urine buffered to a mean pH of 4.6. However, at alkaline pH (mean = 8.1) there was a biphasic degradation of doxorubicin (mean t1/2 = 3.24 and 89 h respectively). The data indicate that buffering intravesical doxorubicin to pH 4.6 (acetate buffer) or pre-dosing of patients with ammonium chloride may minimise loss of active drug during the time for which the drug is retained in the bladder. Recovery of doxorubicin following 1 hour's retention in the bladder was similar (77%) for doses of 38/48 or 78 mg. It is suggested that a dose of 50 mg (1 mg/ml) is sufficient to ensure an adequate delivery of active drug to the bladder wall.
Ilett
K F
KF
Combined Unit in Clinical Pharmacology and Toxicology, University of Western Australia, Nedlands.
Ong
R T
RT
Batty
K T
KT
Taylor
J D
JD
D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use / Q000652:urine*; D004355:Drug Stability; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D004317:Doxorubicin