Pharmacokinetic study of cerebrospinal fluid penetration of cis-diamminedichloroplatinum (II)

Gormley, Paul E.; Gangji, Diamon; Wood, James H.; Poplack, David G.

doi:10.1007/bf00434394

Cited by 29 publications

(7 citation statements)

References 6 publications

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“…The CSF penetration of cisplatin in our model is similar to a prior study (18), but the CSF penetration of carboplatin is lower than previous reports (8 -10). The disparity between our study and these previous reports with carboplatin may be related to the limited number CSF samples measured in prior studies.…”

Section: Discussionsupporting

confidence: 86%

Plasma and Cerebrospinal Fluid Pharmacokinetics of Intravenous Oxaliplatin, Cisplatin, and Carboplatin in Nonhuman Primates

Jacobs

Fox

Dennie

et al. 2005

Clinical Cancer Research

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Purpose: Describe and compare the central nervous system pharmacology of the platinum analogues, cisplatin, carboplatin, and oxaliplatin and develop a pharmacokinetic model to distinguish the disposition of active drug from inert platinum species.Experimental Design: Oxaliplatin (7 or 5 mg/kg), cisplatin (2 mg/kg), or carboplatin (10 mg/kg) was given i.v. Serial plasma and cerebrospinal fluid (CSF) samples were collected over 24 hours. Plasma ultrafiltrates were prepared immediately. Platinum concentrations were measured using atomic absorption spectrometry. Areas under the concentration Â Â Â time curve were derived using the linear trapezoidal method. CSF penetration was defined as the CSF AUC 0-24 /plasma ultrafiltrate AUC 0-24 ratio. A four-compartment model with first-order rate constants was fit to the data to distinguish active drug from inactive metabolites.Results: The mean F F SD AUCs in plasma ultrafiltrate for oxaliplatin, cisplatin, and carboplatin were 61 F F 22, 18 F F 6, and 211 F F 64 Mmol/L hour, respectively. The AUCs in CSF were 1.2 F F 0.4 Mmol/L hour for oxaliplatin, 0.56 F F 0.08 Mmol/L hour for cisplatin, and 8 F F 2.2 Mmol/L hour for carboplatin, and CSF penetration was 2.0%, 3.6%, and 3.8%, respectively. For oxaliplatin, cisplatin, and carboplatin, the pharmacokinetic model estimated that active drug accounted for 29%, 79%, and 81% of platinum in plasma ultrafiltrate, respectively, and 25%, 89%, and 56% of platinum in CSF, respectively. The CSF penetration of active drug was 1.6% for oxaliplatin, 3.7% for cisplatin, and 2.6% for carboplatin.Conclusions: The CSF penetration of the platinum analogues is limited. The pharmacokinetic model distinguished between active drug and their inactive (inert) metabolites in plasma and CSF.

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Section: Discussionsupporting

confidence: 86%

Plasma and Cerebrospinal Fluid Pharmacokinetics of Intravenous Oxaliplatin, Cisplatin, and Carboplatin in Nonhuman Primates

Jacobs

Fox

Dennie

et al. 2005

Clinical Cancer Research

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“…The highest concentrations are found in the kidneys, liver, ovaries, uterus, and prostate gland (LeRoy et al 1979;Stewart et al 1982a). Low concentrations are achieved in cerebrospinal fluid, indicating poor penetration into the central nervous system (Gormley et al 1981). However, cisplatin may selectively distribute into intracerebral tumours, and has been reported to have antitumour activity for central nervous system neoplasms (Stewart et al…”

Section: Distributionmentioning

confidence: 96%

Pharmacokinetics of Anticancer Drugs in Children

Crom

Glynn-Barnhart

Rodman

et al. 1987

Clinical Pharmacokinetics

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Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.

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“…However, according to another study [15], CDDP penetrates the cerebrospinal fluid space at a rate of 2.5 % of the maximum plasma concentration when administered intravenously at high doses. We found that 30-40% of the drug at tumor level is distributed in the brain adjacent to the tumor site, where the blood-brain barrier is intact, when high doses (100mg/sq m) are administered intravenously (Nakagawa et al, submitted for publication).…”

Section: Discussionmentioning

confidence: 97%

Cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer

et al. 1993

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Parenchymal brain tumors, which were metastases of primary lung cancer, were surgically removed from 25 patients. During the operation, patients were administered (intravenous or intracarotid) 100 mg/sq m of cis-diamminedichloroplatinum (CDDP) and postoperatively, they received intravenous CDDP at 3-month intervals for 1 year. The results of this mode of treatment were compared with those obtained in 25 patients who underwent the same surgery but received other anticancer agents and in 39 patients who received no postoperative chemotherapy. Patients in the CDDP-treated group survived much longer than both of the other treatment groups. In the CDDP, but not in the other two groups, survival was significantly longer in patients who had undergone resection of their lung tumors than in those who had not. The stage of lung cancer was not found to significantly influence survival time among CDDP-treated patients. Brain metastasis was the cause of death in 12% of the patients who received CDDP, in 16% those treated with other drugs, and in 26% of those who received no chemotherapy. The incidence of local and remote intracranial tumor recurrence, including meningeal carcinomatosis, was similar in the three groups. However, the mean interval from resection of the metastatic brain tumor to local or remote recurrence was longer in the CDDP-treated group than in the other two groups, and the 2-year-survival rate was significantly higher after CDDP administration. These results suggest that CDDP may be useful in the therapy of metastatic brain tumors derived from lung cancer.

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Pharmacokinetic study of cerebrospinal fluid penetration of cis-diamminedichloroplatinum (II)

Cited by 29 publications

References 6 publications

Plasma and Cerebrospinal Fluid Pharmacokinetics of Intravenous Oxaliplatin, Cisplatin, and Carboplatin in Nonhuman Primates

Plasma and Cerebrospinal Fluid Pharmacokinetics of Intravenous Oxaliplatin, Cisplatin, and Carboplatin in Nonhuman Primates

Pharmacokinetics of Anticancer Drugs in Children

Cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer

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