TY - JOUR
T1 - Clinical pharmacology of homoharringtonine
AU - Savaraj, N.
AU - Lu, K.
AU - Dimery, I.
AU - Feun, L. G.
AU - Burgess, M.
AU - Keating, M.
AU - Loo, T. L.
PY - 1986/12/1
Y1 - 1986/12/1
N2 - Clinical pharmacology of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 μCi) 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 [3H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an α-half-life of 0.5 ± 0.1 hours and a β-half-life of 9.3 ± 1.4 hours. The total clearance of HHT was 177.4 ± 27.7 ml·hour-1·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·kg-1. Correspondingly, the total [3H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3H was 67.5 ± 7.5 hours, 7.4 times longer; the total clearance was 30.9 ± 3.1 ml·hour-1·kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 ± 0.1 L·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.
AB - Clinical pharmacology of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 μCi) 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 [3H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an α-half-life of 0.5 ± 0.1 hours and a β-half-life of 9.3 ± 1.4 hours. The total clearance of HHT was 177.4 ± 27.7 ml·hour-1·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·kg-1. Correspondingly, the total [3H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3H was 67.5 ± 7.5 hours, 7.4 times longer; the total clearance was 30.9 ± 3.1 ml·hour-1·kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 ± 0.1 L·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.
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M3 - Article
C2 - 3791253
AN - SCOPUS:0022885441
VL - 70
SP - 1403
EP - 1407
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 12
ER -