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Pharmacokinetic and pharmacodynamic studies with mitoxantrone in the treatment of patients with nasopharyngeal carcinoma
Author(s) -
Hu Oliver YoaPu,
Chang ShiuPei,
Law ChiKong,
Jian JerMin,
Chen KuangYao
Publication year - 1992
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19920215)69:4<847::aid-cncr2820690402>3.0.co;2-l
Subject(s) - medicine , mitoxantrone , nasopharyngeal carcinoma , pharmacodynamics , pharmacokinetics , oncology , carcinoma , pharmacology , chemotherapy , radiation therapy
The pharmacokinetics and pharmacodynamics of mitoxantrone were studied in 15 patients with advanced nasopharyngeal carcinoma (NPC) after single intravenous rapid infusion (12 to 14 mg/m 2 ). Mitoxantrone plasma concentrations and urinary excretion were measured specifically with the use of a high‐performance liquid chromatographic method with ultraviolet detection at 242 and 658 nm. The pharmacokinetic parameters are described adequately by a three‐compartment model with a terminal half‐life of 71.5 ± 40.1 hours and a volume of distribution of 5037 ± 2377 l0. The total plasma clearance was 743 ± 462 ml/minute, and the renal clearance was 18.8 ± 8.49 ml/minute. Within 72 hours, 1.8 ± 0.6% of the administration dose was excreted in urine as mitoxantrone parent compound. From the urinary excretion rate data, glomerular filtration and possible tubular reabsorption were the mechanisms involved in the urinary excretion of mitoxantrone. The values for unbound fraction (%) in plasma at time 0 and 5 minutes were 2.88 ± 0.91% and 3.25 ± 1.19%, with an average of 3.04 ± 1.01%. The degree of protein binding of mitoxantrone was not affected by concentration (P > 0.05) in Chinese patients with NPC. The response rate for mitoxantrone was poor in this study. Clinical studies have demonstrated that mitoxantrone was generally well tolerated. Only very low incidences of nausea, vomiting, and alopecia were observed. The mild and rapidly reversible dose‐limiting hematologic toxic effects have proven leukopenia. Although the toxicities reported here were tolerated for most patients, other combination regimens including mitoxantrone or other administration routes may be considered and need to be evaluated carefully. Cancer 1992; 69:847–853.