Comparative pharmacokinetics of chlorambucil and melphalan in man.

David S Alberts, S. Y. Chang, H. S. Chen, B. J. Larcom, T. L. Evans

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3-4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil's greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictable alkylating agent for clinical use than melphalan, especially for patients with reduced renal function.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalRecent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
Volume74
StatePublished - 1980
Externally publishedYes

Fingerprint

Chlorambucil
Melphalan
Pharmacokinetics
Mustard Plant
Alkylating Agents
Hematologic Neoplasms
Tablets
Kidney
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Comparative pharmacokinetics of chlorambucil and melphalan in man. / Alberts, David S; Chang, S. Y.; Chen, H. S.; Larcom, B. J.; Evans, T. L.

In: Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer, Vol. 74, 1980, p. 124-131.

Research output: Contribution to journalArticle

@article{db479ba27b544558aa396546911d2e94,
title = "Comparative pharmacokinetics of chlorambucil and melphalan in man.",
abstract = "We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3-4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil's greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictable alkylating agent for clinical use than melphalan, especially for patients with reduced renal function.",
author = "Alberts, {David S} and Chang, {S. Y.} and Chen, {H. S.} and Larcom, {B. J.} and Evans, {T. L.}",
year = "1980",
language = "English (US)",
volume = "74",
pages = "124--131",
journal = "Recent Results in Cancer Research",
issn = "0080-0015",
publisher = "Springer New York",

}

TY - JOUR

T1 - Comparative pharmacokinetics of chlorambucil and melphalan in man.

AU - Alberts, David S

AU - Chang, S. Y.

AU - Chen, H. S.

AU - Larcom, B. J.

AU - Evans, T. L.

PY - 1980

Y1 - 1980

N2 - We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3-4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil's greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictable alkylating agent for clinical use than melphalan, especially for patients with reduced renal function.

AB - We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3-4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil's greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictable alkylating agent for clinical use than melphalan, especially for patients with reduced renal function.

UR - http://www.scopus.com/inward/record.url?scp=0019283629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019283629&partnerID=8YFLogxK

M3 - Article

C2 - 7444135

AN - SCOPUS:0019283629

VL - 74

SP - 124

EP - 131

JO - Recent Results in Cancer Research

JF - Recent Results in Cancer Research

SN - 0080-0015

ER -