"The findings, published online April 4 and in the May issue of Obstetrics Gynecology, should reassure physicians who are reluctant to prescribe HT in these patients out of concern it might increase the risk for recurrence and reduce surviv"...
Plasma concentrations of the parent compound, cisplatin (cisplatin injection) , decay monoexponentially with a half-life of about 20 to 30 minutes following bolus administration of 50 or 100 mg/m2 doses. Monoexponential decay and plasma half-lives of about 0.5 hour are also seen following two hour or seven hour infusions of 100 mg/m2. After the latter, the total-body clearances and volumes of distribution at steady-state for cis-platin are about 15 to 16 L/h/m2 and 11 to 12 L/m2.
Due to its unique chemical structure, the chlorine atoms of cisplatin (cisplatin injection) are more subject to chemical displacement reactions by nucleophiles, such as water or sulfhydryl groups, than to enzyme-catalyzed metabolism. At physiological pH in the presence of 0.1M NaCl, the predominant molecular species are cisplatin (cisplatin injection) and monohydroxymonochloro cis-diammine platinum (II) in nearly equal concentrations. The latter, combined with the possible direct displacement of the chlorine atoms by sulfhydryl groups of amino acids or proteins, accounts for the instability of cisplatin (cisplatin injection) in biological matrices. The ratios of cisplatin (cisplatin injection) to total free (ultrafilterable) platinum in the plasma vary considerably between patients and range from 0.5 to 1.1 after a dose of 100 mg/m2.
Cisplatin (cisplatin injection) does not undergo the instantaneous and reversible binding to plasma proteins that is characteristic of normal drug-protein binding. However, the platinum from cisplatin (cisplatin injection) , but not cisplatin (cisplatin injection) itself, becomes bound to several plasma proteins including albumin, transterrin, and gamma globulin. Three hours after a bolus injection and two hours after the end of a three-hour infusion, 90% of the plasma platinum is protein bound. The complexes between albumin and the platinum from cisplatin (cisplatin injection) do not dissociate to a significant extent and are slowly eliminated with a minimum half-life of five days or more.
Following cisplatin (cisplatin injection) doses of 20 to 120 mg/m2, the concentrations of platinum are highest in liver, prostate, and kidney, somewhat lower in bladder, muscle, testicle, pancreas, and spleen and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum. Platinum is present in tissues for as long as 180 days after the last administration. With the exception of intracerebral tumors, platinum concentrations in tumors are generally somewhat lower than the concentrations in the organ where the tumor is located. Different metastatic sites in the same patient may have different platinum concentrations. Hepatic metastases have the highest platinum concentrations, but these are similar to the platinum concentrations in normal liver. Maximum red blood cell concentrations of platinum are reached within 90 to 150 minutes after a 100 mg/m2 dose of cisplatin (cisplatin injection) and decline in a biphasic manner with a terminal half-life of 36 to 47 days.
Over a dose range of 40 to 140 mg cisplatin (cisplatin injection) /m2 given as a bolus injection or as infusions varying in length from 1 hour to 24 hours, from 10% to about 40% of the administered platinum is excreted in the urine in 24 hours. Over five days following administration of 40 to 100 mg/m2 doses given as rapid, 2 to 3 hour, or 6 to 8 hour infusions, a mean of 35% to 51% of the dosed platinum is excreted in the urine. Similar mean urinary recoveries of platinum of about 14% to 30% of the dose are found following five daily administrations of 20, 30, or 40 mg/m2/day. Only a small percentage of the administered platinum is excreted beyond 24 hours post-infusion and most of the platinum excreted in the urine in 24 hours is excreted within the first few hours. Platinum-containing species excreted in the urine are the same as those found following the incubation of cisplatin (cisplatin injection) with urine from healthy subjects, except that the proportions are different.
The parent compound, cisplatin (cisplatin injection) , is excreted in the urine and accounts for 13% to 17% of the dose excreted within one hour after administration of 50 mg/m2. The mean renal clearance of cisplatin (cisplatin injection) exceeds crea-tinine clearance and is 62 and 50 mL/min/m2 following administration of 100 mg/m2 as 2 hour or 6 to 7 hour infusions, respectively.
The renal clearance of free (ultrafilterable) platinum also exceeds the glomerular filtration rate indicating that cisplatin (cisplatin injection) or other platinum-containing molecules are actively secreted by the kidneys. The renal clearance of free platinum is nonlinear and variable and is dependent on dose, urine flow rate, and individual variability in the extent of active secretion of possible tubular reabsorption.
There is a potential for accumulation of ultrafilterable platinum plasma concentrations whenever cisplatin (cisplatin injection) is administered on a daily basis but not when dosed on an intermittent basis.
No significant relationships exist between the renal clearance of either free platinum or cisplatin (cisplatin injection) and creatinine clearance.
Last reviewed on RxList: 6/13/2008
This monograph has been modified to include the generic and brand name in many instances.
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