title: [Melphalan pharmacokinetics during isolated limb regional perfusion in patients with skin melanoma and soft tissue sarcoma].
abstract: The study of pharmacokinetics of melphalan in the perfusate and blood plasma during isolated limb regional perfusion (ILRP) was carried out in patients with melanoma (n=21) and soft tissue sarcoma (n = 24). Melphalan was administered as 10 mg/l for a lower extremity and 13 mg/l for a upper extremity. Quantification of melphalan in perfusate and blood samples was performed by means of liquid chromatography/tandem mass spectrometry. 30 samples of the perfusate and 27 venous blood samples were analyzed. During the first 5 minutes of ILRP concentration of melphalan in the perfusate decreased to 13.2% of the initial value, and by the end of perfusion (60 minutes) it was 3.3%. The amount of melphalan in the blood plasma of the patients by the end of ILRP wasn't higher than 1.6% from the administered dose. That demonstrates minor systemic absorption of the drug during ILRP. Moreover melphalan concentration in the blood plasma during the perfusion was in average 0.015-0.223 mg/l which is significantly lower compared to the blood plasma concentrations after intravenous administration of melphalan. Thus ILRP procedure provided 97% of the melphalan dose accumulation in the soft tissues of a limb and in tumor tissues. Also pharmacokinetic advantage of melphalan over systemic administration of the drug was shown.
authors.forename: G I
authors.initials: GI
authors.lastname: Gafton
authors.forename: K Yu
authors.initials: KY
authors.lastname: Senchik
authors.forename: V G
authors.initials: VG
authors.lastname: Petrov
authors.lastname: V V Semiglazov
authors.lastname: N V Tatyanicheva
authors.lastname: V G Bespalov
authors.forename: Yu V
authors.initials: YV
authors.lastname: Semiletova
authors.forename: I G
authors.initials: IG
authors.lastname: Gafton
authors.forename: G V
authors.initials: GV
authors.lastname: Zinoviev
authors.forename: G S
authors.initials: GS
authors.lastname: Kireeva
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D010478:Chemotherapy, Cancer, Regional Perfusion; D002853:Chromatography, Liquid; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008558:Melphalan / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008875:Middle Aged; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D000096142:Cutaneous Malignant Melanoma
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan