PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “PLATINUM”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1985

In vivo distribution studies of radioactively labelled platinum complexes; cis-dichlorodiammine platinum(II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum(IV), cis-dichloro-bis-cyclopropylamine platinum(II), and cis-diammine 1,1-cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera.

The in vivo distribution in man of the four platinum derivatives cis-dichlorodiammine platinum(II) (DDP), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (IV) (CHIP), cis-dichloro-bis-cyclopropylamine platinum(II) (CP), and cis-diammine 1, 1-cyclobutanedicarboxylate platinum(II) (CBDCA) has been observed. The availability of these compounds labelled with the radioactive isotope of platinum, platinum-191, has made serial in vivo imaging of their distribution possible. Injection of 17-35 MBq (5-28 mg) of the labelled compound IV was followed by imaging, using a gamma camera, with particular reference to the kidneys, liver, and tumour site. Hepatic and renal clearances were observed in all nine patients, but no unequivocal evidence of tumour uptake was found. The left kidney uptake was estimated at times up to 7 days after injection. Mathematical analysis of some of the uptake curves failed to show any significant difference between the clearance times observed. However, the two patients who received CBDCA did show a higher initial renal uptake, falling within the 1st day to levels comparable with those of the other compounds, and the three patients who received DDP showed consistently liver uptake.

Adult↗
PubMed1982

Blood clearance of three radioactively labelled platinum complexes: cis-dichlorodiammine platinum II, cis, trans-dichlorodihydroxy-bis-(isopropylamine) platinum IV, and cis-dichloro-bis-cyclopropylamine platinum II, in patients with malignant disease.

The blood clearances of three platinum compounds, cis-dichlorodiammine platinum II (DDP), cis, trans-dichloro-dihydroxy-bis-(isopropylamine) platinum IV (CHIP), and cis-dichloro-bis-cyclopropylamine platinum II (CP), were determined in nine patients with malignant disease. The complexes were prepared using radioactive platinum (191Pt and 193Pt). A 10-mu Ci dose of each complex, containing the equivalent of 1-2 mg elemental platinum, was injected IV into groups of three patients. Serial blood and urine samples were collected over 72 h. No obvious difference was found between the three complexes for blood clearance, median t1/2a being 16.8 (range 11.2-23.5) min and median t1/2 beta 89 (range 63.7-127) h. The urinary excretion was greatest for CHIP, 60% of injected dose as against 42.6% for CP and 38.8% for DDP. Differences in renal excretion of DDP analogues could indicate potentially less nephrotoxic agents. The use of radioactive Pt will allow in vivo dynamic imaging of the distribution of platinum compounds in areas of interest.

Aged↗
PubMed1994

Preclinical toxicology and tissue platinum distribution of novel oral antitumour platinum complexes: ammine/amine platinum(IV) dicarboxylates.

The preclinical toxicology and tissue platinum distribution of a series of six orally given antitumour platinum complexes [ammine/amine platinum(IV) dicarboxylates] with structural variations of their alicyclic amine (c-C5, c-C6 or c-C7), axial dicarboxylate (CH3, C3H7 or NHC2H5) or leaving substituents (Cl2 or OCOOCO) was studied in the mouse. Platinum tissue levels measured at 48 h after a single oral dose at 0.5 of the MTD were highest in the liver (6.0-19 micrograms/g) and second highest in the kidney (2.8-12 micrograms/g), and these levels were up to 5 times higher than those reported with equi-toxic doses of i.v. cisplatin and i.v. carboplatin. Platinum levels in the lung, heart, spleen, skin, skeletal muscle and brain were all < or = 3.1 micrograms/g at this dose level. Liver platinum levels measured at 2 h, 2 days, 6 days and 10 days after a single oral dose at the MTD ranged widely (from 15 to 109 micrograms platinum/g), were related to the number of carbon atoms in the axial dicarboxylate and alicyclic amine groups (r = 0.9389) and showed a diversity of time-course profiles. Elevations of plasma ALT activity were recorded with single oral doses of JM225 and JM256 at the MTD. Accumulation of platinum in the liver with repeated oral dosing weekly for 4 consecutive weeks at 0.5 of the MTD occurred with JM269 (3.3-fold increase, P < 0.05) and JM225 (2.4-fold increase, P < 0.05), and elevated plasma ALT activity (44 +/- 33 IU/l) was recorded with repeated oral doses of JM269. JM216 was selected from this series of analogues for further study on the basis of the elevated plasma ALT activity (JM225, JM256 and JM269), liver platinum accumulation (JM269 and JM225), poor activity against human ovarian carcinoma xenografts (JM291) or severe emetogenesis (JM221) of other examples. Following a single oral dose of JM216 at the MTD, transient reductions in the WBC (nadir, 1.6 x 10(9)/l, 2 days, 74% reduction), platelet count (nadir, 613 x 10(9)/l, 10 days, 33% reduction) and bone marrow cellularity (nadir, 0.5 x 10(7) nucleated cells/femur, 4 days, 75% reduction) were found, and these had recovered by 21 days after treatment. Jejunal mucosal disaccharidase activity following single MTDs indicated that small-intestinal mucosal damage was less severe for oral JM216 (nadir maltase activity, 68% +/- 16% of control, NS) than for i.v. cisplatin (nadir maltase activity).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1981

Heterogeneous platinum-catalyzed hydrogenation of dialkyl(diolefin)platinum(II) complexes: A new route to platinum surface alkyls.

Platinum metal catalyzes the reduction of dialkyl(diolefin)platinum(II) complexes by dihydrogen to alkanes and platinum(0). The reaction involves adsorption of the platinum(II) complex on the platinum(0) catalyst surface with conversion of the alkyl moieties to platinum surface alkyls; these appear as alkane products. The platinum atom originally present in the soluble organoplatinum species becomes part of the platinum(0) surface.

Journal Article↗
PubMed2002

X-ray structures of the first platinum complexes with Z configuration iminoether ligands: trans-dichlorobis(1-imino-1-methoxy-2,2'-dimethylpropane)platinum(II) and trans-tetrachlorobis(1-imino-1-methoxy-2,2'-dimethylpropane)platinum(IV).

Platinum complexes with Z configuration iminoether ligands (trans-[PtCl(2)(HN=C(OMe)Bu(t))(2)], 1, and trans-[PtCl(4)(HN=C(OMe)Bu(t))(2)], 2) have been structurally characterized for the first time. The nearly planar Pt-N-C-O-C chain, all atoms being in gauche conformation, brings the terminal Pt and C atoms very close to one another. The steric clash is released by considerably increasing the Pt-N-C, N-C-O, and C-O-C bond angles (133, 124, and 121 degrees for 1, respectively; 147, 129, and 127 degrees for 2, respectively), which are well above the expected values (120 degrees for Pt-N-C and N-C-O; less than 120 degrees for C-O-C owing to the repulsive effect exerted by the lone pair of electrons on the oxygen atom). In the platinum(II) case the smaller increase of bond angles is accompanied by a greater value of the Pt-N-C-O torsion angle (27.3 and 15.6 degrees for 1 and 2, respectively). The stabilization of the Z configuration, notwithstanding the steric clashes described above, has been achieved by a careful choice of the R substituent in the iminoether moiety (a bulky tert-butyl group). The reactions of the platinum(IV) species (2) in basic and acidic conditions and with triphenylphosphine have been investigated. Bases and acids both interact with the coordinated ligand in such a way to weaken the coordinative bond and promote the release of the iminoether ligands. The phosphine promotes a ready and complete reduction of the platinum(IV) complex to the corresponding platinum(II) species (1). Compound 1 reacts with a stoichiometric amount of phosphine (1:1 molar ratio) to form cis-[PtCl(2)(PPh(3))(Z-HN=C(OMe)Bu(t))] and with excess phosphine to form [PtCl(2)(PPh(3))(2)] and free iminoether. The latter two reactions leading to formation of a mixed phosphine/iminoether platinum species and to free iminoether, which can be used as a synthon for further organic transformations, can be of synthetic utility.

Journal Article↗
PubMed1990

[Pharmacokinetics of cis-diammine (glycolato) platinum (254-S), a new platinum antitumor agent, following an intravenous and intraperitoneal infusion bioactive platinum concentration profile].

The pharmacokinetics of cis-diammine (glycolato) platinum (254-S) was investigated in cancer patients following intravenous and intraperitoneal infusion. The serum concentrations of total and unbound 254-S were determined by bioassay and chemical assay as platinum. Platinum detected by bioassay was thought to be active and unchanged 254-S. Almost all of platinum in plasma were found to be active and unbound to protein because of no differences in the concentrations determined by bioassay and chemical assay and in plasma and plasma filtrate. In abdominal ascites, platinum concentrations determined by bioassay corresponded with those determined by chemical assay, suggesting that 254-S was stable in abdominal ascites. The Cmax and AUC of active 254-S in plasma determined by bioassay following an intraperitoneal infusion were about 60% and 60-80% of those following an intravenous infusion, respectively. These results showed that 254-S was well absorbed into systemic circulation from abdominal ascites as an active form. It is concluded that antitumor effect may be obtained following an intraperitoneal infusion of 254-S as well as for the reduction of abdominal ascites.

Aged↗
PubMedDate not supplied

Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP), in mice.

(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice. DWA2114R was effective against murine tumor lines, Colon 26 and Colon 38 carcinomas, M5076 ovarian sarcoma and P388 L1210 leukemias, implanted subcutaneously (s.c.). Triple injection every other day of DWA2114R was more effective than a single injection at each sublethal dose. The antitumor effects of DWA2114R against these tumors were more effective than or were similar to those of CBDCA and CDDP. The antitumor effect against CDDP-resistant L1210 leukemia implanted s.c. was only observed in the treatment of DWA2114R, but not in CBDCA and CDDP. No excellent antitumor effects of three platinum complexes were observed against Lewis lung carcinoma and B16 melanoma implanted s.c. even at triple injection every other day, and no effect was obtained against Meth-A fibrosarcoma under similar conditions. While the treatment of CDDP showed marked increases in levels of blood urea nitrogen and of urinary protein and sugar at effective doses in the antitumor evaluations, the treatment of DWA2114R as well as CBDCA showed no increase in these parameters. These results indicate that DWA2114R represents a desirable second generation antitumor platinum complex.

Animals↗
PubMed1992

Estrogen platinum-diamine complexes: preparation of a non-steroidal estrogen platinum-diamine complex labeled with platinum-191 and a study of its binding to the estrogen receptor in vitro and its tissue distribution in vivo.

We have prepared in radiolabeled form (platinum-191) a non-steroidal estrogen platinum-diamine complex (Pt-diamine complex) that is reported to have selective cytostatic activity in estrogen receptor positive mouse mammary tumors. We then studied the interaction of this metal radiolabeled complex with the estrogen receptor in vitro and its distribution in immature rats in vivo. The radiolabeled complex was prepared by incubation of the non-steroidal estrogen diamine with [191Pt](II)Cl(-2)4 (t 1/2 = 2.96 days, sp. act. 7.54 Ci/mmol) in dimethylformamide (DMF)/H2O, followed by purification by HPLC. The final radiolabeled product coeluted with an authentic standard of the unlabeled Pt-diamine complex, with a retention time distinct from those of the precursor diamine and chloroplatinate. In competitive radiometric receptor binding assays with rat uterine estrogen receptor, samples of the unlabeled diamine and Pt-diamine complex have apparent binding affinities of 53 +/- 3% and 32 +/- 11%, respectively, relative to estradiol (RBA = 100% as standard). However, attempts to observe the binding of the 191Pt-diamine complex with the estrogen receptor were complicated by a very high level of non-receptor binding, an irreversible binding to proteins in the receptor preparation, and a degradation of the platinum complex that, in part, releases the diamine. As a result, it is difficult to be certain whether the binding affinity measured for the Pt-diamine complex in the competitive binding assays is due to the complex itself, or whether it arises from diamine released upon degradation of the complex. In tissue distribution studies in immature female rats, much of the 191Pt-diamine complex was deposited in the liver; there was no evidence of selective uptake of this compound by estrogen target tissues. Thus, it is not clear, from these studies, that the observed bioactivity of this complex arises from the interaction of the Pt complex or the diamine ligand with the estrogen receptor.

Animals↗
PubMed1989

Water-soluble third generation antitumor platinum complexes, [2,2-bis (aminomethyl)-1,3-propanediol-N,N']-[1,1-cyclobutanedicarboxylato (2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O'] [tetrahydro-4H-pyran-4,4-dimethanamine-N,N']platinum(II).

The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-pyran-4,4- dimethanamine-N,N'-)platinum(II) have shown the greatest promise for further investigation and are currently under clinical evaluation.

Animals↗
PubMed1983

Sister chromatid exchanges induced by two radiosensitizing platinum compounds (cis-dichloro-bis isopropylamine trans dihydroxy platinum IV (CHIP) and cis platinum metronidazole2Cl2(FLAP)) in CHO cells in vitro.

Sister chromatid exchange (SCE) induction by two radiosensitizing platinum compounds (cis-dichloro-bis isopropylamine trans dihydroxy platinum IV (CHIP) and cis-platinum metronidazole2 Cl2 (FLAP] was studied in CHO cells in vitro. Both drugs induced SCE in a dose dependent manner. CHIP was a much more potent inducer of SCE than FLAP and produced almost 4 times as many SCE as FLAP at equimolar concentrations and twice as many at equitoxic dosage. Induction of SCE by a component of the FLAP molecule--metronidazole--was also examined. It did not cause any increase of SCE frequency over the control level when applied at 10 times the highest concentration of FLAP which was used.

Animals↗
PubMed2002

Platinum complexes of oxopurines: cis-bis(theophyllinato-N7)bis(triphenylphosphine)platinum(II) and cis-chloro(theobrominato-N1)bis(triphenylphosphine)platinum(II) ethanol hemisolvate.

The syntheses and structures of two mixed-ligand complexes of platinum(II) with deprotonated oxopurine bases and triphenylphosphine are reported, namely the theophyllinate complex cis-bis(1,2,3,6-tetrahydro-1,3-dimethylpurine-2,6-dionato-kappaN(7))bis(triphenylphosphine-kappaP)platinum(II), [Pt(C(7)H(7)N(4)O(2))(2)(C(18)H(15)P)(2)], (I), and the theobrominate complex cis-chloro(1,2,3,6-tetrahydro-3,7-dimethylpurine-2,6-dionato-kappaN(1))bis(triphenylphosphine-kappaP)platinum(II) ethanol hemisolvate, [PtCl(C(7)H(7)N(4)O(2))(C(18)H(15)P)(2)].0.5C(2)H(5)OH, (II). In (I), the coordination geometry of Pt is square planar, formed by the two coordinating N atoms of the theophyllinate anions in a cis arrangement and two P atoms from the triphenylphosphine groups. In (II), there are two crystallographically independent molecules. They both exhibit a square-planar coordination geometry around Pt involving one Cl atom, the coordinating N atom of the theobrominate anion and two P atoms from the triphenylphosphine groups. The two triphenylphosphine groups are arranged in a cis configuration in both structures. The heterocyclic rings are rotated with respect to the coordination plane of the metal by 82.99(8) and 88.09(8) degree in complex (I), and by 85.91(16) and 88.14(18) degree in complex (II). Both structures are stabilized by intramolecular stacking interactions involving the purine rings and the phenyl rings of adjacent triphenylphosphine moieties.

Antineoplastic Agents↗
PubMed1987

Platinum group metal sensitivity: reactivity to platinum group metal salts in platinum halide salt-sensitive workers.

The ability of closely related platinum group metal salts (PGMS) to cross-react with the principal sensitising agent ammonium hexachloroplatinate IV was investigated in refinery workers. Selected subjects were screened by skin prick test, specific RAST, RAST inhibition, and primate PCA tests. These showed--but only in platinum-sensitive subjects--a low prevalence of skin and RAST sensitivity to the other PGMS and limited evidence of hapten specific cross-reactivity.

Animals↗
PubMed1989

Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparison with cis-platinum and carboplatinum.

A new platinum complex, oxalatoplatin or l-OHP, which, at the same metal dose in experimental tests is as efficient as cisplatin, and is more so at a lower metal dose than carboplatin; which is as efficient in human tumors of the testis and ovary as these other analogs, and more so in melanoma and breast cancer; which is not nephrotoxic, cardiotoxic or mutagenic, and hardly hematotoxic and neurotoxic, is described and compared with the above-mentioned platinum complexes. Combined with 5Fu, it induces a high number of remissions in colorectal cancer, and has brought about cures in inoperable gastric cancers. Combined with carboplatin, it has resulted in a high proportion of cures in L1210-carrying mice, which no other two-by-two combination of these complexes has achieved.

Animals↗
PubMed2006

Synthesis and characterization of amidate bridged dimeric and oligomeric platinum complexes having short platinum-platinum interactions.

A number of pivalamidate bridged dinuclear [PtII2(RNH2)4(NHCOtBu)2]2+, [PtIII2LL (RNH2)4(NHCOtBu)2]n+ (2RNH2 = 2NH3, 1,2-ethylenediamine, 1,2-diaminocyclohexane; L, L' = NO3-, H2O, or ketonate), trinuclear [{PtII(dap)(NHCOtBu)2}2PdIII]3+ (dap = 1,2-diaminopropane), tetranuclear [{PtII2(NH3)2(DACH)(NHCOtBu)2}2]4+ (DACH = 1,2-diaminocyclohexane), pentanuclear [{Pt2(C5H7O)(NH3)2Cl2(NHCOtBu)2}2PtCl4], and hexanuclear [Pt2(NH3)2(en)(NHCOtBu)2Pt(NO2)4]2 platinum complexes containing Pt(II)-Pt(II), Pt(II)-Pt(III), Pt(II)-Pd(III), and Pt(III)-Pt(III) interactions have been prepared and structurally characterized. The Pt-Pt interactions are characteristic of covalent, dative, or orbital symmetric Pt-Pt bonds. The dimeric Pt(III) complexes are able to activate C-H bonds of ketones to afford ketonate platinum(III) complexes. The Pt-Pt bonds are either doubly amidate-bridged or ligand unsupported. Their distances are 2.99-3.22 A for Pt(II)-Pt(II), 2.59-2.72 A for Pt(III)-Pt(III), 2.98 A for Pt(II)-Pt(III), and 2.66 A for Pt(II)-Pd(III) bonds depending on the oxidation states of the two metals and the ancillary ligands.

Journal Article↗
PubMed2004

Structures of platinum(II) complexes of 2-aminomethylaziridine and S-2-aminomethylazetidine and correlation of anticancer activities of (2-aminomethylazacycloalkane)platinum(II) complexes with the geometry of the chelate rings formed with platinum(II).

The spectroscopic properties of platinum(II) complexes with 2-aminomethyl-derivatives of small-membered 1-aza-cycloalkane, i.e., =2-aminomethylaziridine=azida and S-2-aminomethylazetidine=S-azeda, and the crystal structures of their dichloro complexes demonstrate that the conformation of the fused three- (azida) or four- (S-azeda) and five-membered chelate ring formed by the coordination of S-azida and S-azeda to platinum(II) has an S(N) absolute configuration at the secondary amine site and that the two alkyl groups extend axially from the five-membered chelate ring. The chelate ring of the azida is more planar than the S-azeda or other 2-aminomethyl-1-azacycloalkanes. The anticancer activity reported for azeda and 2-aminomethylpyrrolidine appears to be related to their coordination structure, namely the presence of cis-fused successive rings.

Antineoplastic Agents↗
PubMed1991

Shikimic acid complexes of platinum. Preparation, reactivity, and antitumor activity of (R,R-1,2-diaminocyclohexane) bis(shikimato) platinum(II). Evidence for a novel rearrangement involving platinum-carbon bond formation.

The complex (R,R-1,2-diaminocyclohexane)bis(shikimato)platinum(II) (shikimato = the anion of 3R,4S,5R-trihydroxy-1-cyclohexene-1-carboxylic acid), I, has been synthesized and purified by high performance liquid chromatography (HPLC). The complex is only moderately stable in aqueous solution. Its major hydrolysis product, also purified by HPLC, is proposed to be a unique complex type in which a single shikimate group is coordinated through both the carboxylate oxygen and the C(2) vinylic carbon of the shikimate moiety [Pt(R,R-dach)(O,C-shikimato)], II. In vitro, complex I is active against L1210 leukemia and against an L1210 cell line with acquired resistance to cisplatin. In vivo, the complex is active against L1210, P388, and B16 melanoma; this activity is highly schedule-dependent. Complex II is also active against L1210 leukemia.

Animals↗
PubMed2003

Platinum retreatment of platinum-resistant ovarian cancer after nonplatinum therapy.

OBJECTIVE: The objective was to determine the response rate to platinum retreatment of "platinum-resistant" ovarian cancer after intervening nonplatinum therapy. METHODS: We retrospectively identified 30 patients with platinum-resistant ovarian cancer who received nonplatinum chemotherapy for recurrent epithelial ovarian cancer prior to additional platinum therapy. All patients were treated between July 1, 1997, and June 30, 2001. Platinum resistance was defined as less than a partial response to platinum therapy or progression within 6 months of the last platinum therapy. RESULTS: Overall, 7 of 30 patients experienced an objective response to platinum therapy (partial response, 23%; complete response, 0%) based on CT scan (2/21) and/or CA-125 (5/9) criteria. The median time to progression for the group was 17 weeks (range, 4-59 weeks). Several predictive factors were identified. The interval since the last platinum treatment did not appear to be predictive in this group. Only 1 of 16 patients who did not have an objective response to the most recent platinum-based therapy responded to platinum rechallenge. Similarly, no patient who received more than three intervening nonplatinum treatments responded to additional platinum therapy (0/10). CONCLUSIONS: Our small retrospective series suggest that the platinum-resistant category is heterogenous and includes patients who may respond to retreatment with platinum-based agents. This group includes the patients with prior platinum responses and early progression. However, patients without an objective response to the last prior platinum therapy or more than three intervening treatments are unlikely to respond to subsequent platinum therapy.

Adult↗