Disposition of orally administered 14C-prednimustine in cancer patients

Gaver, Robert C.; Deeb, G. Michael; Pittman, Kenneth A.; Issell, Brian F.; Mittelman, Arnold; Smyth, Robert D.

doi:10.1007/bf00254192

Cited by 10 publications

(2 citation statements)

References 12 publications

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“…While chlorambucil, its metabolite, phenylacetic acid mustard, and prednisolone are easily detected, intact prednimustine could not be observed in plasma after oral administration of the drug in previous pharmacokinetic studies [5,8,17,18,28,[31][32][33][34], Some studies indicate that prednimustine is incompletely absorbed by the gastrointestinal tract. While the bio availability of chlorambucil and prednisolone is more than 70% [7.…”

Section: Discussionmentioning

confidence: 99%

Comparative Pharmacokinetics of Chlorambucil and Prednimustine after Oral Administration

Loos

Musch²,

Malek³

et al. 1991

Oncology

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The pharmacokinetics of chlorambucil, phenylacetic acid mustard (the β-oxidation product of chlorambucil), and prednisolone were investigated in a cross-over study after oral administration of chlorambucil (30 mg) + prednisolone (50 mg) versus prednimustine (300 mg), the ester of chlorambucil and prednisolone. Intact prednimustine could not be detected in plasma at any time. After administration of prednimustine, the plasma concentration-time curves of chlorambucil, phenylacetic acid mustard, and prednisolone showed a retarded profile compared to the administration of the single components. The mean bioavailability was 14% for chlorambucil, 21% for phenylacetic acid mustard, and 22% for prednisolone, when given as prednimustine, compared to the administration of free compounds in stoichiometrically equivalent doses. When given in the oral dosages mentioned above, the average dose-intensity was 62% for chlorambucil, 95% for phenylacetic acid mustard, and 72% for prednisolone, indicating sufficient therapeutic concentrations of the detectable agents.

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Section: Discussionmentioning

confidence: 99%

Comparative Pharmacokinetics of Chlorambucil and Prednimustine after Oral Administration

Loos

Musch²,

Malek³

et al. 1991

Oncology

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“…Sterecyt | (prednimustine) is a chlorambucil ester of prednisolone which combines alkylating and glucocorticoid properties. The efficacy following oral administration of Sterecyt | is most likely due to chlorambucil and/or prednisolone or metabolites of the compounds [ 14]. The pharmacokinetics of Sterecyt | showed that a lower peak of chlorambucil from Sterecyt | was found in vivo as well as in vitro [15].…”

Section: Introductionmentioning

confidence: 97%

Mitoxantrone in combination with prednimustine in treatment of unfavorable non-Hodgkin lymphoma

Landys

1988

Invest New Drugs

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Mitoxantrone (Novantrone) and prednimustine (Sterecyt) are both active as single agents in the treatment of unfavorable non-Hodgkin lymphoma (UNHL). The efficacy and toxicity of the combination of these agents (NOSTE) was evaluated in 28 patients with advanced histopathologically proven UNHL who were not eligible for aggressive conventional chemotherapy. The median age was 68, range 45-84. Sixteen patients were previously untreated. Eleven patients had received doxorubicin or epidoxorubicin containing regimens and 1 patient had received CVP as first line therapy. MUGA scan was used in monitoring cardiac function in patients with cardiac risk. Novantrone was administered at a dose of 8 mg/m2 IV on days 1 and 2 and Sterecyt as an absolute dose 100 mg/less than or equal to 1.6 m2-150 mg/greater than 1.6 m2 on days 1 through 5. The regimen was repeated every 4th week. The number of courses per patient ranged from 2 to 10. Objective response was obtained in 22 (78%) patients (20 CR and 2 PR). No response occurred in 6 patients (4 SD, 2 PD). Decreased left ventricular ejection fraction was recorded in 1 patient who suffered from asthma and ischemic heart disease. Hematological toxicity was tolerable. Gastrointestinal toxicity was rare. No hair loss was observed. After a median follow-up of 28 months the crude survival was 46%. Twelve of twenty complete responders are still in remission, the median duration of remission is 28.3 months, range 15-37. NOSTE in this pilot study showed a high response rate, good tolerance and mild toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Oppitz

Musch

Malek

et al. 1989

Cancer Chemother. Pharmacol.

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Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the beta-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednisolone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil. Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects of prednimustine demonstrated by clinical studies.

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Disposition of orally administered 14C-prednimustine in cancer patients

Cited by 10 publications

References 12 publications

Comparative Pharmacokinetics of Chlorambucil and Prednimustine after Oral Administration

Comparative Pharmacokinetics of Chlorambucil and Prednimustine after Oral Administration

Mitoxantrone in combination with prednimustine in treatment of unfavorable non-Hodgkin lymphoma

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

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