A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients

  title={A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients},
  author={Lars Bastholt and Carl J. Johansson and Per Pfeiffer and Leif D Svensson and S A Johansson and Per Olov Gunnarsson and Henning T. Mouridsen},
  journal={Cancer Chemotherapy and Pharmacology},
SummaryThe pharmacokinetic characteristics of prednisolone and of chlorambucil and its β-oxidized metabolite, phenylacetic mustard (PAM) were studied in plasma after the oral administration of 200 mg prednimustine (Sterecyt) and a regimen consisting of 20 mg prednisolone plus 20 mg chlorambucil, respectively. A total of 12 cancer patients completed this trial. The drugs were given in a cross-over study as single doses, and serial plasma samples were collected for 32 h. Chlorambucil and PAM were… 
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Population pharmacokinetics identifies rapid gastrointestinal absorption and plasma clearance of oral chlorambucil administered to cats with indolent lymphoproliferative malignancies.

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, and these data are critical to inform future work investigating the association of chlor Ambucil drug exposure with adverse events and outcome of cats with lymphoproliferative diseases.

Synthesis, in vivo antileukemic evaluation and comparative study of novel 5alpha-7-keto steroidal esters of chlorambucil and its active metabolite.

The reduction of the double bond had a negative impact on the antileukemic potency since the comparative study of the novel derivatives showed that a series of very potent Delta 5-7-keto-steroidal esters were converted by this modification to compounds with marginally accepted activity.

Reactions of 4-bis(2-chloroethyl)aminophenylacetic acid (phenylacetic acid mustard) in physiological solutions

According to the present results 2 is decomposed in aqueous solutions by the same mechanism as other aromatic and aliphatic nitrogen mustards: an intramolecular, rate determining attack of the unprotonated nitrogen to form an aziridinium ion intermediate is followed by attack of an external nucleophile.

Reactions of {4‐[Bis(2‐chloroethyl)amino]phenyl}acetic Acid (Phenylacetic Acid Mustard) with 2′‐Deoxyribonucleosides

Phenylacetic acid mustard (PAM) was found to be hydrolytically slightly more stable than CLB and the role of PAM–2′‐deoxyribonucleoside adducts on the cytotoxic and mutagenic properties of CLB is discussed.



Studies on the pharmacokinetics of chlorambucil and prednimustine in man.

Research aimed at producing chlorambucil analogues, which cannot be metabolised, seems justified, and the use of prednimustine in routine combination therapy is not recommended.

Studies on the pharmacokinetics of chlorambucl and prednimustine in patients using a new high-performance liquid chromatographic assay

A new high-performance liquid chromatographic assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml and found the pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambuccil and prednisolone together.

The pharmacokinetics of prednimustine and chlorambucil in the rat

The reduced toxicity of prednimustine is due to chlorambucil esterification and the subsequent alteration in pharmacokinetics, whilst inhibition of alkylating agent-resistant tumours results from the combination of chlor Ambucil and prednisolone.

Cytotoxicity and metabolism of prednimustine, chlorambucil and prednisolone in a Chinese hamster cell line

Prednimustine and chlorambucil induce dose-and time-dependent cell death in V79 Chinese hamster cells in vitro and it appears that the prolonged availability of chlorambUCil is responsible for the increased potency of prednimUSTine in this system.

Prednisolone plasma levels after oral administration of Prednimustine. Comparison with levels obtained after administration of an equimolar dose of prednisolone.

After oral administration of 100 mg Prednimustine to patients with metastatic breast carcinoma, prednisolone levels and the area under the plasma concentration-time curve between 2 and 24 h are

Pharmacokinetics of chlorambucil in man after administration of the free drug and its prednisolone ester (prednimustine, Leo 1031)

The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug and its prednisolone ester and no intact prednimustine could be detected in plasma.

Mammary tumour inhibition and subacute toxicity in rats of prednimustine and of its molecular components chlorambucil and prednisolone.

This study showed that the mortality, reduction of lymphocytes and platelets, and bone marrow depression was much lower after pregnimustine than after equimolar amounts of the C + P combination.

Inter- and intraindividual differences in oral chlorambucil pharmacokinetics

Inter- and intraindividual variation in the pharmacokinetics of oral chlorambucil was investigated in patients with chronic lymphocytic leukaemia, and the AUC of the metabolite was higher and showed twofold interindividual variation.

Disposition of orally administered 14C-prednimustine in cancer patients

Although prednimustine was well absorbed, the ester was subject to extensive presystemic metabolism and was not present in the systemic circulation after oral administration, and it was eliminated slowly with an estimated terminal elimination half-life of about 10 days.