title: Determination of plicamycin in plasma by radioimmunoassay.
abstract: This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials.
authors.affiliation: Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: K
authors.initials: K
authors.lastname: Fang
authors.forename: C A
authors.initials: CA
authors.lastname: Koller
authors.forename: N
authors.initials: N
authors.lastname: Brown
authors.forename: W
authors.initials: W
authors.lastname: Covington
authors.forename: J R
authors.initials: JR
authors.lastname: Lin
authors.forename: D H
authors.initials: DH
authors.lastname: Ho
mesh_terms: D000918:Antibody Specificity; D003429:Cross Reactions; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism; D008926:Plicamycin / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics; D011863:Radioimmunoassay
chemical_list: D007457:Iodine Radioisotopes; C066851:mithramycin A; D008926:Plicamycin