Dosing of carboplatin in a patient with amputated legs: A case report.

Carboplatin is a platinum derivative that is commonly used in combination chemotherapy for treatment of several malignancies, including small-cell lung carcinoma (SCLC). Because the estimated glomerular filtration rate, and therefore the carboplatin dose, is based on the serum creatinine level, dosing of carboplatin for amputees is a challenge. This case report describes how serum carboplatin levels were used to determine the most suitable carboplatin dose for an amputee. The patient received four cycles of etoposide in combination with carboplatin area under the curve = 5 mg·min/ml, with a dose reduction of 25% and concurrent radiotherapy. The measured area under the curve was found to be 3.41 mg·min/ml, while the target area under the curve was 3.75 mg·min/ml (75% of 5 mg·min/ml). Therefore, for the next cycles, the carboplatin dose was calculated using the Calvert formula. No recurrence of disease was seen within two years after completion of therapy. This case demonstrates that therapeutic drug monitoring can successfully be used to determine the carboplatin dose for an amputee.

Ciprofloxacin strongly inhibits clozapine metabolism: two case reports.

We report on two cases of drug-drug interactions between ciprofloxacin and clozapine. The first case was a 46-year-old male patient receiving a daily dose of clozapine 900 mg. He was admitted to hospital with urosepsis and was treated with a 5-day course of ciprofloxacin and amoxicillin. Two days after completion of antibacterial therapy, the patient developed symptoms of rhabdomyolysis. Clozapine therapy was discontinued and measurement of the patient's clozapine plasma concentration 1 day after cessation of clozapine therapy and 3 days after cessation of ciprofloxacin treatment showed that it was in excess of recommended therapeutic levels. The second patient was a 58-year-old male patient treated with a daily dose of clozapine 300 mg. He was admitted to hospital because of delirium and suspected urinary tract infection or pneumonia. Treatment with ciprofloxacin was initiated. Measurement of clozapine plasma concentrations prior to and 3 days after commencement of ciprofloxacin showed that clozapine concentrations doubled over that time period. We suggest that inhibition of cytochrome P450 (CYP) enzymes 1A2 and 3A4 by ciprofloxacin resulted in delayed clozapine metabolism and elevated clozapine plasma concentrations. This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin.

Inductively coupled plasma mass spectrometric analysis of the total amount of platinum in DNA extracts from peripheral blood mononuclear cells and tissue from patients treated with cisplatin.

We present a highly sensitive method for the determination of platinum (Pt) in DNA extracts of peripheral blood mononuclear cells (PBMCs) and tissue samples from patients treated with cisplatin. The method is based on the measurement of Pt by inductively coupled plasma mass spectrometry (ICP-MS) and allows quantification of Pt-DNA adducts in PBMCs isolated from 10 mL blood and 1 mg tissue. The lower limit of quantification is 0.75 pg Pt or 7.5 fg Pt µg(-1) DNA when using 100 µg DNA. The method proved to be accurate and precise. The results obtained using the ICP-MS method were in good agreement with results from the alternative (32)P-postlabelling assay. The ICP-MS method was, however, more sensitive and proved to be less laborious. The advantages of the presented ICP-MS technique were demonstrated by the analysis of PBMCs, normal gastric tissue, and gastric tumour tissue of patients treated with cisplatin.

Sensitive inductively coupled plasma mass spectrometry assay for the determination of platinum originating from cisplatin, carboplatin, and oxaliplatin in human plasma ultrafiltrate.

We present a highly sensitive, rapid method for the determination of platinum originating from the anticancer agents cisplatin, carboplatin, and oxaliplatin in human plasma ultrafiltrate. The method is based on the quantification of platinum by inductively coupled plasma mass spectrometry and allows quantification of 7.50 ng l-1 platinum in only 150 microl of matrix. Sample pretreatment involves dilution of samples with 1% HNO3. Validation fulfilled the most recent FDA guidelines for bioanalytical method validation. Validated ranges of quantification were 7.50 ng l-1 to 1.00x10(5) ng l-1 in plasma ultrafiltrate for all three platinum compounds. The assay is now successfully used to support pharmacokinetic studies in cancer patients treated with cisplatin, carboplatin, or oxaliplatin.

Inductively coupled plasma mass-spectrometric determination of platinum in excretion products of client-owned pet dogs.

Residues of antineoplastic drugs in canine excretion products may represent exposure risks to veterinary personnel, owners of pet dogs and other animal care-takers. The aim of this study was to measure the extent and duration of platinum (Pt) excretion in pet dogs treated with carboplatin. Samples were collected before and up to 21 days after administration of carboplatin. We used validated, ultra-sensitive, inductively coupled plasma-mass spectrometry assays to measure Pt in canine urine, faeces, saliva, sebum and cerumen. Results showed that urine is the major route of elimination of Pt in dogs. In addition, excretion occurs via faeces and saliva, with the highest amounts eliminated during the first 5 days. The amount of excreted Pt decreased over time but was still quantifiable at 21 days after administration of carboplatin. In conclusion, increased Pt levels were found in all measured excretion products up to 21 days after administration of carboplatin to pet dogs, with urine as the main route of excretion. These findings may be used to further adapt current veterinary guidelines on safe handling of antineoplastic drugs and treated animals.

Determination of platinum surface contamination in veterinary and human oncology centres using inductively coupled plasma mass spectrometry.

The objective of this study was to determine the surface contamination with platinum-containing antineoplastic drugs in veterinary and human oncology centres. Inductively coupled plasma mass spectrometry was used to measure platinum levels in surface samples. In veterinary and human oncology centres, 46.3 and 68.9% of the sampled surfaces demonstrated platinum contamination, respectively. Highest platinum levels were found in the preparation rooms (44.6 pg cm(-2)) in veterinary centres, while maximal levels in human centres were found in oncology patient-only toilets (725 pg cm(-2)). Transference of platinum by workers outside areas where antineoplastic drugs were handled was observed in veterinary and human oncology centres. In conclusion, only low levels of platinum contamination attributable to carboplatin were found in the sampled veterinary oncology centres. However, dispersion of platinum outside areas where antineoplastic drugs were handled was detected in veterinary and human oncology centres. Consequently, not only personnel, but also others may be exposed to platinum.

Monitoring of platinum surface contamination in seven Dutch hospital pharmacies using inductively coupled plasma mass spectrometry.

OBJECTIVE: To develop, validate, and apply a method for the determination of platinum contamination, originating from cisplatinum, oxaliplatinum, and carboplatinum. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine platinum in wipe samples. The sampling procedure and the analytical conditions were optimised and the assay was validated. The method was applied to measure surface contamination in seven Dutch hospital pharmacies. RESULTS: The developed method allowed reproducible quantification of 0.50 ng l(-1) platinum (5 pg/wipe sample). Recoveries for stainless steel and linoleum surfaces ranged between 50.4 and 81.4% for the different platinum compounds tested. Platinum contamination was reported in 88% of the wipe samples. Although a substantial variation in surface contamination of the pharmacies was noticed, in most pharmacies, the laminar-airflow (LAF) hoods, the floor in front of the LAF hoods, door handles, and handles of service hatches showed positive results. This demonstrates that contamination is spread throughout the preparation rooms. CONCLUSION: We developed and validated an ultra sensitive and reliable ICP-MS method for the determination of platinum in surface samples. Surface contamination with platinum was observed in all hospital pharmacies sampled. The interpretation of these results is, however, complicated.

Determination of oxaliplatin in human plasma and plasma ultrafiltrate by graphite-furnace atomic-absorption spectrometry.

A method for sensitive determination of the anti-cancer agent oxaliplatin in human plasma and human plasma ultrafiltrate (pUF) is presented. The method is based on the quantification of platinum by graphite-furnace atomic-absorption spectrometry, with Zeeman correction and an atomisation temperature of 2,700 degrees C. Sample pretreatment involves dilution of the samples with a solution containing 0.15 mol L(-1) NaCl and 0.20 mol L(-1) HCl in water. Validation was performed in accordance with the most recent FDA guidelines for bioanalytical method validation. All results were within requirements. The validated ranges of quantification were 0.10-400 micromol L(-1) for human pUF and 0.50-400 micromol L(-1) for plasma. The assay is now successfully used to support pharmacokinetic studies of cancer patients treated with oxaliplatin.