A phase I trial of marcellomycin with a weekly dose schedule

Joss, R; Kaplan, S.; Goldhirsch, Aron; Varini, M.; Brunner, K. W.; Cavalli, Franco

doi:10.1016/0277-5379(83)90106-2

Cited by 6 publications

(3 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Marcellomycin (MCM) is a new class II anthracycline antitumor antibiotic that was introduced into clinical trials mainly because of its lack of myelosuppression in the animal models used in the preclinical evaluation of this drug [4,18]. Unfortunately, hopes were disappointed, in that myelosuppression was the major dose-limiting toxicity in the two clinical trials conducted with this drug [13,15]. In addition, myelosuppression was erratic and unpredictable.…”

Section: Discussionmentioning

confidence: 99%

“…Patients and sample collections. Pharmacokinetic parameters were determined in nine cancer patients, six men and three women, aged 30-68 years (median: 58 years) who were entered in two phase-1 trials [13,15]. All had advanced disease not amenable to control by surgery, radiation therapy, hormonal therapy, or conventional chemotherapeutic agents.…”

Section: Chemicals and Reagents Silica Gel 60 Plates (250 ~Tm) Werementioning

confidence: 99%

“…However, in the two clinical trials conducted so far, myelosuppression was the major and dose-limiting toxicity of MCM [13,15]. In addition, the myelotoxicity of MCM was Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human pharmacokinetics of marcellomycin

Dodion

Rozencweig

Nicaise

et al. 1985

Cancer Chemother. Pharmacol.

View full text Add to dashboard Cite

In conjunction with two phase I clinical trials, we have investigated the pharmacokinetics of marcellomycin (MCM), a new class II anthracycline antibiotic, in nine patients with normal renal and hepatic functions and no third-space fluid accumulation. MCM was infused IV over 15 min at a dosage of 27.5, 40, or 50 mg/m2. Plasma and urine samples were collected up to 72 h. MCM and metabolites were assayed by thin-layer chromatography and quantified by specific fluorescence. The disappearance of total MCM-derived fluorescence from plasma followed first-order kinetics and lacked the rebound in total fluorescence that has been described for the structurally similar agent, aclacinomycin A. After 40-50 mg/m2, the peak MCM concentration in plasma was 1.67 +/- 0.61 microM; MCM disappeared from plasma in a triexponential fashion and was undetectable by 48 h after infusion. The area under the plasma concentration-time plot (AUC), including the infusion time, was 1.11 +/- 0.39 microM X h; plasma clearance of MCM was 1.50 +/- 0.88 l/min/m2. Five other fluorescent compounds were consistently observed in plasma. M2 was a contaminant present in the parent drug. P1 and P2 were conjugates of MCM and M2, respectively. G1 and G2 were aglycones. The peak concentrations of the metabolites were 25% or less or the peak concentration for MCM, but their persistence resulted in higher AUCs than that for MCM. For the dosage of 27.5 mg/m2, fewer data were available; but the pharmacokinetics of MCM and metabolites appeared to be similar to that at higher dosage. Urinary excretion of total fluorescence amounted to 8.0% +/- 1.6% of the total dose at 40-50 mg/m2, and to 7.0% +/- 2.3% at 27.5 mg/m2. No correlation was detected among the various pharmacokinetic parameters and toxicities encountered in these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Chemicals and Reagents Silica Gel 60 Plates (250 ~Tm) Werementioning

confidence: 99%

See 1 more Smart Citation

Human pharmacokinetics of marcellomycin

Dodion

Rozencweig

Nicaise

et al. 1985

Cancer Chemother. Pharmacol.

View full text Add to dashboard Cite

show abstract

Desorption chemical ionization mass spectrometry of anthracyclines and of trisaccharides related to aclacinomycin a and marcellomycin

Monneret

Sellier

1986

Biol. Mass Spectrom.

View full text Add to dashboard Cite

Desorption chemical ionization mass spectrometry with ammonia as the reagent gas was used to obtain positive ion spectra of twelve alkyl-anthraquinones, seven anthracyclinones, eleven anthracycline antibiotics and nine oligosaccharides (di- and trisaccharides). Ions corresponding to the intact molecules (M) were present in all spectra as pseudo-molecular ions [M + H]+ and/or [M + NH]+. However, the most significant results were obtained in the case of anthracyclines and oligosaccharides. With anthracyclines, in addition to the preceding ions, spectra exhibited characteristic fragment ions due to the aglycon or to the sugar moiety while ions corresponding to the sequential loss of monosaccharide units were observed with oligosaccharides. All these fragment ions can be readily explained by an initial site of protonation located at the oxygen atom of the glycosidic linkages.

show abstract

Comparative murine metabolism and disposition of class II anthracycline antibiotics

Dodion

Egorin

Riggs

et al. 1985

Cancer Chemother. Pharmacol.

View full text Add to dashboard Cite

The metabolism and tissue distribution of aclacinomycin A (ACL), marcellomycin (MCM), and musettamycin (MST), three new anthracycline antibiotics, were compared after IV administration to mice. In plasma, total MCM- and ACL-derived fluorescence declined according to first-order kinetics, whereas an initial decline followed by a rebound was observed for MST. In plasma, MCM remained the predominant compound. ACL was eliminated more quickly, and was replaced by two metabolites, the reduced glycoside M1, and an aglycone. In the case of MST, two unidentified metabolites were observed in concentrations equivalent to that of the parent drug. The three drugs were distributed widely to organs, but only ACL achieved measurable concentrations in the brain. Initially, high concentrations of all three drugs were present in the lungs, but these decreased quickly to values similar to those present in the liver and kidneys. Intermediate concentrations of the three drugs were measured in heart and skeletal muscle. Splenic concentrations of all three drugs rose progressively, reaching a maximum at 8 h after injection in the case of ACL and MST, and at 24 h after injection in the case of MCM. Concentrations of the metabolites of MCM and MST were low in all organs except liver and kidney, where the aglycones 7-deoxypyrromycinone and bisanhydropyrromycinone were seen. The metabolism of ACL was extensive. Aglycones were dominant in the liver and kidneys, whereas reduced glycosides predominated in the spleen. These observations indicate that the murine pharmacology of these three structurally similar drugs differs markedly.

show abstract

A phase I trial of marcellomycin with a weekly dose schedule

Cited by 6 publications

References 3 publications

Human pharmacokinetics of marcellomycin

Human pharmacokinetics of marcellomycin

Desorption chemical ionization mass spectrometry of anthracyclines and of trisaccharides related to aclacinomycin a and marcellomycin

Comparative murine metabolism and disposition of class II anthracycline antibiotics

Contact Info

Product

Resources

About