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A F LeRoy

Publications and source records attributed to A F LeRoy.

8 recordsLinked to original sources
PubMed1989

Binding kinetics of tetrachloro-1,2-diaminocyclohexaneplatinum (IV) (tetraplatin) and cis-diamminedichloroplatinum (II) at 37 degrees C with human plasma proteins and with bovine serum albumin. Does aquation precede protein binding?

Experiments were conducted at 37 degrees C to study the kinetics of (a) binding of cis-diamminedichloroplatinum (II) (CDDP) and of a racemic mixture of d- and l-isomers of trans-tetrachloro-1,2-diaminocyclohexaneplatinum (IV) [or tetraplatin (TP)] to protein [human plasma proteins or bovine serum albumin (BSA)]; (b) aquation (acid hydrolysis) of CDDP and of TP; and (c) binding of charged (aquated) CDDP species to BSA. The experiments were performed at clinically relevant concentrations for CDDP, so that the proportional concentrations of platinum complexes relative to the concentrations of other chemical species in blood plasma were similar to those obtaining in the clinical use of the drug. "Free" (unbound) platinum complexes were separated from the protein-bound complexes were separated from the protein-bound complexes by gel filtration chromatography. By use of ion-exchange chromatography, charged platinum species were separated from the uncharged species and free charged platinum species of CDDP were separated from those bound to BSA. Platinum in various fractions was quantitated by atomic absorption spectrophotometry with electrothermal atomization; proteins were quantitated by te Bradford method with Coomassie blue dye. The kinetic data obtained by the application of these methods for CDDP are in good agreement with those obtained by other methods, e.g., binding rates based on separations by centrigugal ultrafiltration. The overall protein-binding reaction of CDDP was consistent with a binding process comprising two consecutive first-order reaction steps: the rate-controlling aquation reaction [half-life (t 1/2), approximately 2 hr] followed by a more rapid binding reaction of the charged (aquated) CDDP species to the protein (t 1/2, approximately 23 min). However, the results for TP indicated that prior aquation was not required for protein binding, and we could surmise that binding of TP to protein proceeds via a direct nucleophilic attack. An unexpected finding was the marked, reproducible difference in rates of aquation between the two lots of TP that we used; this finding suggests the need for cautions evaluation of pharmacokinetic data describing the behavior of TP.

Antineoplastic Agents↗
PubMed1979

Kinetics of cis-dichlorodiammineplatinum.

The cancer chemotherapeutic cis-dichlorodiammineplatinum (cis-DDP) was administered to 8 patients (1-hr intravenous infusion) at a dose of 70 mg/m2. Plasma and urine concentrations of platinum were determined by flameless atomic absorption spectrometry. Measured plasma platinum concentrations revealed a biphasic clearance of platinum with half-life values of 23 min and 67 hr. Platinum values obtained 3 wk after the infusion indicated that a third excretory phase might be present. Urinary measurements showed 17 +/- 2.7% of the administered dose excreted in the first 4 hr and 23 +/- 3.9% excreted in the first 24 hr. Renal excretion appears to be predominantly by glomerular filtration. Non-protein-bound plasma platinum values were calculated and the non-protein-bound platinum was found to be rapidly and biphasically cleared from the plasma with half-life values of 8 to 10 min and 40 to 45 min.

Animals↗
PubMed1975

Interactions of platinum metals and their complexes in biological systems.

Platinum-metal oxidation catalysts are to be introduced in exhaust systems of many 1975 model-year automobiles in the U.S. to meet Clean Air Act standards. Small quantities of finely divided catalyst have been found issuing from prototype systems; platinum and palladium compounds may be found also. Although platinum exhibits a remarkable resistance to oxidation and chemical attack, it reacts chemically under some conditions producing coordination complex compounds. Palladium reacts more readily than platinum. Some platinum-metal complexes interact with biological systems as bacteriostatic, bacteriocidal, viricidal, and immunosuppressive agents. Workers chronically exposed to platinum complexes often develop asthma-like respiratory distress and skin reactions called platinosis. Platinum complexes used alone and in combination therapy with other drugs have recently emerged as effective agents in cancer chemotherapy. Understanding toxic and favorable interactions of metal species with living organisms requires basic information on quantities and chemical characteristics of complexes at trace concentrations in biological materials. Some basic chemical kinetic and thermodynamic data are presented to characterize the chemical behavior of the complex cis-[Pt(NH3)2Cl2] used therapeutically. A brief discussion of platinum at manogram levels in biological tissue is discussed.

Animals↗
PubMedDate not supplied

Disposition and distribution of platinum following parenteral administration of cis-dichlorodiammineplatinum(II) to animals.

After iv administration of cis-dichlorodiammineplatinum(II) (cis-platinum) to animals, plasma levels of platinum decline in a biphasic manner, with a distribution phase (alpha) half-life of minutes and an elimination phase (beta) half-life of days. Urinary excretion of platinum is extensive on the first day after drug administration with a final urinary recovery of 70%--90% of the administered dose. Platinum is initially distributed to nearly all tissues with the highest levels appearing in kidney, liver, ovary, uterus, skin, and bone. There is no preferential uptake of platinum into tumor, although the presence of a tumor may alter the rate of platinum excretion and the extent of whole-body retention. No effect is seen on hepatic microsomal drug metabolism after ip administration of cis-platinum to rats. Platinum is excreted more rapidly from hydrated animals than from controls although total urinary recovery of platinum is nearly equal in both groups. Most analogs of cis-platinum appear to follow the same elimination and distribution patterns as cis-platinum itself.

Animals↗