Plasma concentrations of carminomycin and carminomycinol in man, measured by high pressure liquid chromatography

Lankelma, J.; Penders, Paul G.M.; McVie, J. G.; Leyva, A.; Bokkel‐Huinink, W. W. Ten; Planque, M M de; Pinedo, H.M.

doi:10.1016/0277-5379(82)90007-4

Cited by 13 publications

(4 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma samples were extracted according to a modification of a procedure developed for carminomycin (CMM) (8). To one ml plasma samples carminomycin was added as internal standard (50 or 250 ng/ml), to correct for differences in extraction efficiency.…”

Section: Sample Clean-upmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of 4′-epi-doxorubicin in man

et al. 1983

Self Cite

View full text Add to dashboard Cite

The pharmacokinetics of 4'-epi-doxorubicin (4'-epi-adriamycin, 4'-epi-DX) in man can be described by a three-compartment model with a rapid distribution phase and a very long elimination phase. Urine excretion amounts to a total of about 11% of the administered dose during 48 h after drug administration, and less than 1% during the following 48 h. In plasma 4'-epi-doxorubicin is rapidly converted to five metabolites (4'-epi-doxorubicinol, aglycones and glucuronides), the concentration of the aglycones sometimes exceeding that of 4'-epi-DX. In urine only three metabolites were found in addition to the parent drug; they were identified as 4'-epi-doxorubicinol (EOH), 4'-epi-doxorubicin-glucuronide (E-Glu) and 4'-epi-doxorubicinol-glucuronide (EOH-Glu). Comparison of the pharmacokinetics and metabolic profiles of 4'-epi-DX and doxorubicin (DX) in man revealed that 4'-epi-DX eliminates faster than DX.

show abstract

Section: Sample Clean-upmentioning

confidence: 99%

“…Aqueous solutions of 4'-epi-DX and carminomycin (CMM) are unstable due to light and temperature influences which have been previously described for other anthracyclines (8,9). 4'-Epi-DX and CMM declined to 57% and 28% of the initial concentration (1.8 • 10-4M) respectively after 20 h at 25~ under daylight.…”

Section: Stability Of Solutionsmentioning

confidence: 99%

Pharmacokinetics of 4′-epi-doxorubicin in man

et al. 1983

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, it appears that the metabolism of esorubicin is limited. In contrast, with other anthracycline derivatives such as daunorubicin and daunorubicin analogs, the formation of alcohol derivatives is much more pronounced (22)(23)(24). Variations in the production of alcohol derivatives are related to the ability of these antbracycline antibiotics to function as substrates for the aldoketoreductase (25).…”

Section: Discussionmentioning

confidence: 99%

Human pharmacokinetics of esorubicin (4′ -deoxydoxorubicin)

et al. 1985

View full text Add to dashboard Cite

The pharmacokinetics of esorubicin, a new anthracycline antibiotic, was investigated in conjunction with a phase I clinical trial. The drug was administered to 12 patients as an intravenous bolus at a dose of 20 to 40 mg/m2. All patients had normal renal and hepatic functions and no third space fluid accumulation. Plasma and urine samples were assayed by HPLC. The peak plasma concentration of esorubicin was 0.74 +/- 0.57 microM (mean +/- SE). Esorubicin disappeared from plasma according to a tri-exponential pattern with a terminal half-life of 20.4 +/- 7.3 hr. The area under the plasma concentration versus time curve was 0.64 +/- 0.31 microM x hr. Total body plasma clearance was 45.5 +/- 26.8 liter/min/m2 and the apparent volume of the central compartment, 41.0 +/- 24.8 L. A single metabolite, 4'-deoxydoxorubicinol, was detected in plasma. This metabolite was observed in 5 patients only and its mean peak concentration was 0.029 +/- 0.017 microM. The area under the plasma versus concentration time curve for 4'-deoxydoxorubicinol was 0.02 +/- 0.014 microM xhr. The urinary excretion of total fluorescence within 5 days of therapy was 7.3 +/- 1.3% of the administered dose. Esorubicin represented more than 80% of the excreted anthracyclines. As in plasma, 4'-deoxydoxorubicinol was the only metabolite detectable in urine. No correlation between the various pharmacokinetic parameters and drug-induced toxicity was observed in this small group of patients.

show abstract

“…As compared to doxorubicin, it exerts a 10 to 100 times greater inhibitory effect in vitro against normal human marrow myeloid colony-forming cells (4,5). Clinical pharmacology studies indicate that peak plasma levels average 0.05 #g/ml with areas under the plasma concentration vs. time curves varying between 4 and 57 • 10 -8 M/1/h (4,6). Initial clinical studies yielded promising therapeutic results in various malignancies (7,8), but recent EORTC trials revealed lack of drug activity in breast cancer and soft tissue sarcoma (9,10).…”

Section: Introductionmentioning

confidence: 99%

Phase II study of carminomycin in a human tumor cloning assay

et al. 1984

View full text Add to dashboard Cite

The anticancer activity of carminomycin was investigated in a human tumor cloning assay. No efficacy could be identified in the WiDr and the MCF7 cell lines which were highly responsive to doxorubicin. In addition, drug testing experiments were carried out in samples of various malignancies freshly obtained from 86 patients of whom 54 had not received prior anthracyclines. A reduction in the number of tumor colony forming units by 50% or more was seen in 1/26 breast cancers, 1/22 ovarian cancers and 1/7 melanomas. Cross-resistance studies indicated that eight tumors were responsive to doxorubicin only and one to carminomycin only whereas two were sensitive to both and 73 were resistant to both. This in vitro Phase II study corroborates the disappointing clinical results achieved with carminomycin.

show abstract

Plasma concentrations of carminomycin and carminomycinol in man, measured by high pressure liquid chromatography

Cited by 13 publications

References 4 publications

Pharmacokinetics of 4′-epi-doxorubicin in man

Pharmacokinetics of 4′-epi-doxorubicin in man

Human pharmacokinetics of esorubicin (4′ -deoxydoxorubicin)

Phase II study of carminomycin in a human tumor cloning assay

Contact Info

Product

Resources

About