Clinical pharmacology of homoharringtonine

Journal Article · Mon Dec 01 04:00:00 EST 1986 · Cancer Treat. Rep.; (United States)

OSTI ID:6799132

Savaraj, N; Lu, K; Dimery, I; Feun, L G; Burgess, M; Keating, M; Loo, T L

Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total (/sup 3/H)HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total (/sup 3/H)HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total /sup 3/H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine.

• Research Organization: Univ. of Texas System Cancer Center, Houston
• OSTI ID: 6799132
• Journal Information: Cancer Treat. Rep.; (United States), Journal Name: Cancer Treat. Rep.; (United States) Vol. 12; ISSN CTRRD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BLOOD PLASMA
BODY FLUIDS
CHROMATOGRAPHY
CLEARANCE
COUNTING TECHNIQUES
DISEASES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MATERIALS
METABOLISM
NEOPLASMS
ORGANIC COMPOUNDS
PATIENTS
REACTION KINETICS
SCINTILLATION COUNTING
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URINE
WASTES