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| Clinical data | |
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| Pronunciation | /ˈkɑːrboʊˌplætən/ |
| Trade names | Paraplatin, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a695017 |
| Routes of administration | Intravenous |
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| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | complete[citation needed] |
| Protein binding | Very low |
| Eliminationhalf-life | 1.1-2 hours |
| Excretion | Kidney |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.050.388 |
| Chemical and physical data | |
| Formula | C6H12N2O4Pt |
| Molar mass | 371.256 g·mol−1 |
| 3D model (JSmol) | |
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Carboplatin, sold under the brand nameParaplatin among others, is achemotherapy medication used to treat a number of forms ofcancer.[3] This includesovarian cancer,lung cancer,head and neck cancer,brain cancer, andneuroblastoma.[3] It is administered byinjection into a vein sometimes via aport.[3]
Side effects generally occur.[3] Common side effects includelow blood cell levels, nausea, andelectrolyte problems.[4][3] Other serious side effects includeallergic reactions andmutagenesis. It may becarcinogenic, but further research is needed to confirm this.[3] Use duringpregnancy may result in harm to the baby.[3] Carboplatin is in theplatinum-based antineoplastic family of medications and works by interfering with duplication ofDNA.[3][5]
Carboplatin was developed as a less toxic analogue ofcisplatin.[6] It was patented in 1972 and approved for medical use in 1989.[7] It is on the 2023World Health Organization's List of Essential Medicines.[8]
Carboplatin is used to treat a number of forms ofcancer. This includesovarian cancer,lung cancer,head and neck cancer,brain cancer, andneuroblastoma. It may be used for some types oftesticular cancer butcisplatin is generally more effective.[3] It has also been used to treattriple-negative breast cancer. Carboplatin has also been used foradjuvant therapy of stage 1seminomatous testicular cancer. Research has indicated that it is not less effective than adjuvantradiotherapy for this treatment, while having fewer side effects.[9] This has led to carboplatin based adjuvant therapy being generally preferred over adjuvant radiotherapy in clinical practice.[10]
Relative tocisplatin, the greatest benefit of carboplatin is its reduced side effects, particularly the elimination ofnephrotoxic effects.Nausea andvomiting are less severe and more easily controlled.[11]
The main drawback of carboplatin is itsmyelosuppressive effect. This causes theblood cell andplatelet output of bone marrow in the body to decrease quite dramatically, sometimes as low as 10% of its usual production levels. The nadir of thismyelosuppression usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease inwhite blood cells (neutropenia) can cause complications, and is sometimes treated with drugs likefilgrastim. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitateshospital readmission and treatment withantibiotics.
Carboplatin differs from cisplatin in that it has abidentate dicarboxylate (the ligand is cyclobutane dicarboxylate, CBDCA) in place of the twochlorideligands. Both drugs are in theplatinum-based antineoplastic family of medications. CBDCA and chloride are the labile ligands in these respective drugs. Carboplatin exhibits sloweraquation (replacement of CBDCA by water) and thus slower DNA binding kinetics, although it forms the same reaction productsin vitro at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes inMCF-7 cell lines while exerting their cytotoxic behaviour.[12] The diminished reactivity limits protein-carboplatin complexes, which are excreted. The lower excretion rate of carboplatin means that more is retained in the body, and hence its effects are longer lasting (a retention half-life of 30 hours for carboplatin, compared to 1.5-3.6 hours in the case of cisplatin).
Like cisplatin, carboplatin binds to and cross-links DNA, interfering with the replication and suppressing growth of the cancer cell.[13][14]
Prior to 1989, most carboplatin dosing used body surface area dosing as with other chemotherapy. However, toxicity from treatment was variable, and therefore Professor Hillary Calvert (University of Newcastle) developed a formula to dose carboplatin based on renal function.
Calvert's formula considers the creatinine clearance and the desiredarea under curve.[15] After 24 hours, close to 70% of carboplatin is excreted in the urine unchanged. This means that the dose of carboplatin must be adjusted for any impairment inkidney function.[16]
Calvert formula:
The typical area under the curve (AUC) for carboplatin ranges from 3-7 (mg/ml)*min.[16] GFR (Glomerular Filtration Rate) is a measure or estimate of kidney function. This is either measured, by measuring clearance of a radioisotope or estimated using serum and (sometimes) urine creatine measurements.[17]
The Calvert formula was developed in 18 patients with GFR measurements up to 133ml/min.[16] It's applicability at very high doses of carboplatin has been challenged[18] and in the US the Food and Drug Administration has recommended capping GFR at 125ml/min.[19] This may be more important where dosing is based on calculations using more modern methods of creatinine measurement. The approach is not supported by all clinicians and certainly less so in those treating seminomas.[20]
Cisplatin reacts withsilver nitrate and then cyclobutane-1,1-dicarboxylic acid to form carboplatin.[21]
Carboplatin, a cisplatin analogue, was developed byBristol Myers Squibb and theInstitute of Cancer Research in order to reduce the toxicity of cisplatin.[6][22] It gained U.S.Food and Drug Administration (FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989. Starting in October 2004, generic versions of the drug became available.
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