The Nitrogen Mustards

Highley, Martin; Landuyt, Bart; Prenen, Hans; Harper, Peter; Bruijn, E. A. de

doi:10.1124/pharmrev.120.000121

Cited by 24 publications

(30 citation statements)

References 351 publications

(317 reference statements)

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“…Once absorbed in humans, chlorambucil is metabolized rapidly and extensively in the liver by monodichloroethylation and B-oxidation, forming the metabolite phenylacetic acid mustard (PAAM). 24 Future studies could measure PAAM peak plasma concentration and time to understand more completely the extent of metabolism of the parent drug in a similar study population. Human studies have shown that after oral administration of chlorambucil, metabolism to PAAM is rapid, and exposure to the metabolite is similar to or greater than that of the parent compound.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics identifies rapid gastrointestinal absorption and plasma clearance of oral chlorambucil administered to cats with indolent lymphoproliferative malignancies

Al‐Nadaf

Wittenburg

Skorupski

et al. 2022

ajvr

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OBJECTIVE To establish the pharmacokinetics of a single 2-mg oral dose of chlorambucil in cats with indolent lymphoproliferative malignancies. ANIMALS 24 client-owned cats. PROCEDURES Cats were assigned to 1 of 4 groups, with each group having a total of 3 sample collection time points over 12 hours after receiving a single 2-mg oral dose of chlorambucil. Each time point combined to generate 6 full patient plasma chlorambucil concentration-time curves from the 24 cats. Chlorambucil treatment was continued every other day and a single, variably timed sample collection was obtained on day 14. Population parameter estimates were obtained by nonlinear mixed-effects modeling. Covariates investigated included age, sex, baseline serum cobalamin, study location, weight, and body condition score. RESULTS Chlorambucil administered orally to cats was found to have a peak plasma concentration of approximately 170 ng/mL (SE, 31.1 ng/mL), percent coefficient of variation (%CV) of 18.4% within 15 minutes, and a terminal half-life of 1.8 hours (SE, 0.21 hour; %CV, 12.4). At the 4-hour mark, a smaller secondary peak in plasma chlorambucil was found. Day 14 samples were similar to those of the initial dose. No covariates showed a significant effect in the population model. CLINICAL RELEVANCE In these cats, chlorambucil at a 2-mg dose administered every other day undergoes rapid gastrointestinal absorption and plasma clearance with no drug accumulation between doses. These data are critical to inform future work investigating the association of chlorambucil drug exposure with adverse events and outcome of cats with lymphoproliferative diseases.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics identifies rapid gastrointestinal absorption and plasma clearance of oral chlorambucil administered to cats with indolent lymphoproliferative malignancies

Al‐Nadaf

Wittenburg

Skorupski

et al. 2022

ajvr

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“…Alkylating agents, such as topical mechlorethamine (nitrogen mustard) and oral chlorambucil and cyclophosphamide, have been used in the treatment of MF for more than 50 years ( 60 , 97 , 98 ). These agents binding to DNA, namely at guanine residues, lead to strand breaks and inter-strand cross-linking, impairing DNA replication ( 60 ).…”

Section: Chemotherapymentioning

confidence: 99%

Harnessing the immune system in the treatment of cutaneous T cell lymphomas

et al. 2023

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Cutaneous T cell lymphomas are a rare subset of non-Hodgkin’s lymphomas with predilection for the skin with immunosuppressive effects that drive morbidity and mortality. We are now appreciating that suppression of the immune system is an important step in the progression of disease. It should come as no surprise that therapies historically and currently being used to treat these cancers have immune modulating functions that impact disease outcomes. By understanding the immune effects of our therapies, we may better develop new agents that target the immune system and improve combinatorial treatment strategies to limit morbidity and mortality of these cancers. The immune modulating effect of therapeutic drugs in use and under development for cutaneous T cell lymphomas will be reviewed.

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“…Nitrogen mustards are important alkylating anticancer drugs, which have been used for a variety of solid neoplasms treatment,[ 16 ] especially in lung and breast cancers. [ 17 18 ] Over the past decades, a good deal of modifications have been made in the area of nitrogen mustard agent to improve its therapeutic effect due to its high reactivity and peripheral cytotoxicity. However, little research about the integration of luminophore into the nitrogen mustard-containing structure for imaging as auxiliary functions of therapeutic effect was reported.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of nitrogen mustard-based fluorophores for cell imaging and cytotoxicity studies

Liang¹,

Liang²,

Li³

et al. 2023

J Adv Pharm Technol Res

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The Nitrogen Mustards

Abstract: The nitrogen mustards are important, well-established therapeutic agents that are used to treat a variety of diseases. Their role is continuing to evolve.

Cited by 24 publications

References 351 publications

Population pharmacokinetics identifies rapid gastrointestinal absorption and plasma clearance of oral chlorambucil administered to cats with indolent lymphoproliferative malignancies

Population pharmacokinetics identifies rapid gastrointestinal absorption and plasma clearance of oral chlorambucil administered to cats with indolent lymphoproliferative malignancies

Harnessing the immune system in the treatment of cutaneous T cell lymphomas

Synthesis of nitrogen mustard-based fluorophores for cell imaging and cytotoxicity studies

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