Pharmacokinetics and metabolism of chlorambucil in man: a preliminary report

David S Alberts, Sai Y. Chang, Hsiao Sheng G Chen, Barbara J. Larcom, Stephen E. Jones

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Abstract

A sensitive and specific gas-chromatographic-mass spectrometric (GC-MS) assay for chlorambucil and its major metabolite in biological fluids, phenylacetic acid mustard, has been developed. It has been applied to the study of oral chlorambucil pharmaco-kinetics in 6 patients. The assay has a sensitivity limit of 50 ng/ml and a precision of 94.3±1.3% at a plasma chlorambucil concentration of 200 ng/ml. In vitro chlorambucil recovery is temperature dependent with recovery rate constants at 37°C of k = 0.43 hr-1 for water and k = 0.12 hr-1 for plasma. After an oral bolus dose of 0.6-1.2 mg/kg in 4 patients the mean terminal phase half-life of chlorambucil was 91.7±19.3 min, its mean peak plasma concentration, 1.1±0.6 μg/ml (adjusted to a dose of 0.6 mg/kg) and its mean plasma concentration-time product, 143±102 μg min/ml (adjusted to a dose of 0.6 mg/kg). The urinary excretion of chlorambucil over the first 24 h was 0.54±0.16% and its mean renal clearance was 0.029±0.014 ml/min/kg. The hepatic extraction of chlorambucil in these 4 patients averaged 0.24±0.13. The mean phenylacetic acid mustard plasma terminal phase half-life was approximately 1.6 times greater than that of its parent compound. The mean 24 h metabolite urinary excretion was 0.29±0.16%. This preliminary pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance, and that it is almost completely metabolized, having extremely low urinary excretion.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalCancer Treatment Reviews
Volume6
Issue numberSUPPL. 1
DOIs
StatePublished - 1979

Fingerprint

Chlorambucil
Pharmacokinetics
Mustard Plant
Half-Life
Gases
Kidney
Temperature
Water
Liver

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Urology

Cite this

Pharmacokinetics and metabolism of chlorambucil in man : a preliminary report. / Alberts, David S; Chang, Sai Y.; Chen, Hsiao Sheng G; Larcom, Barbara J.; Jones, Stephen E.

In: Cancer Treatment Reviews, Vol. 6, No. SUPPL. 1, 1979, p. 9-17.

Research output: Contribution to journalArticle

Alberts, David S ; Chang, Sai Y. ; Chen, Hsiao Sheng G ; Larcom, Barbara J. ; Jones, Stephen E. / Pharmacokinetics and metabolism of chlorambucil in man : a preliminary report. In: Cancer Treatment Reviews. 1979 ; Vol. 6, No. SUPPL. 1. pp. 9-17.
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abstract = "A sensitive and specific gas-chromatographic-mass spectrometric (GC-MS) assay for chlorambucil and its major metabolite in biological fluids, phenylacetic acid mustard, has been developed. It has been applied to the study of oral chlorambucil pharmaco-kinetics in 6 patients. The assay has a sensitivity limit of 50 ng/ml and a precision of 94.3±1.3{\%} at a plasma chlorambucil concentration of 200 ng/ml. In vitro chlorambucil recovery is temperature dependent with recovery rate constants at 37°C of k = 0.43 hr-1 for water and k = 0.12 hr-1 for plasma. After an oral bolus dose of 0.6-1.2 mg/kg in 4 patients the mean terminal phase half-life of chlorambucil was 91.7±19.3 min, its mean peak plasma concentration, 1.1±0.6 μg/ml (adjusted to a dose of 0.6 mg/kg) and its mean plasma concentration-time product, 143±102 μg min/ml (adjusted to a dose of 0.6 mg/kg). The urinary excretion of chlorambucil over the first 24 h was 0.54±0.16{\%} and its mean renal clearance was 0.029±0.014 ml/min/kg. The hepatic extraction of chlorambucil in these 4 patients averaged 0.24±0.13. The mean phenylacetic acid mustard plasma terminal phase half-life was approximately 1.6 times greater than that of its parent compound. The mean 24 h metabolite urinary excretion was 0.29±0.16{\%}. This preliminary pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance, and that it is almost completely metabolized, having extremely low urinary excretion.",
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