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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Human pharmacokinetics of marcellomycin.

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.[1]


  1. Human pharmacokinetics of marcellomycin. Dodion, P., Rozencweig, M., Nicaise, C., Watthieu, M., Tamburini, J.M., Riggs, C.E., Bachur, N.R. Cancer Chemother. Pharmacol. (1985) [Pubmed]
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