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Biomedical subjects

P E Kintzel

Publications and source records attributed to P E Kintzel.

11 recordsLinked to original sources
PubMed2001

Prophylaxis for paclitaxel hypersensitivity reactions.

OBJECTIVE: To evaluate clinical literature supporting the prophylactic use of single-dose intravenous dexamethasone to prevent hypersensitivity reactions (HSRs) to paclitaxel infusion. DATA SOURCES: Clinical literature accessed through MEDLINE (from 1986 to 2000). DATA SYNTHESIS: Prophylaxis for paclitaxel-related HSRs generally includes repeated dexamethasone doses beginning 12 hours before paclitaxel, and administration of diphenhydramine plus a histamine2-receptor antagonist 30 minutes before infusion of paclitaxel. Singe-dose intravenous dexamethasone administered with ancillary medications 30 minutes before infusion of paclitaxel has been used to prevent regimen-related HSRs. CONCLUSIONS: Single-dose intravenous dexamethasone can be used in combination with appropriate ancillary medications to prevent paclitaxel-related HSRs.

Anti-Inflammatory Agents↗
PubMed2001

Anticancer drug-induced kidney disorders.

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium thiosulfate and diethyldithiocarbamate. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have occurred with ifosfamide treatment. High dose azacitidine causes renal dysfunction manifested by tubular acidosis, polyuria and increased urinary excretion of electrolytes, glucose and amino acids. Haemolytic uraemia is a rare adverse effect of gemcitabine. Methotrexate can cause increased serum creatinine levels, uraemia and haematuria. Acute renal failure is reported following administration of high dose methotrexate. Urinary alkalisation and hydration confer protection against methotrexate-induced renal dysfunction. Dose-related nephrotoxicity, including acute renal failure, are reported subsequent to treatment with pentostatin and diaziquone. Acute renal failure is a rare adverse effect of treatment with interferon-alpha. Haemolytic uraemic syndrome occurs with mitomycin administration. A mortality rate of 50 to 100% is reported in patients developing mitomycin-induced haemolytic uraemic syndrome. Capillary leak syndrome occurring with aldesleukin therapy can cause renal dysfunction. Infusion-related hypotension during infusion of high dose carmustine can precipitate renal dysfunction.

Antimetabolites, Antineoplastic↗
PubMed1995

Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function.

The narrow therapeutic index of anticancer drugs presents a clinical dilemma when these agents are administered to patients with impaired or unstable renal function. The purpose of this review is to (i) describe the nephrotoxicity of certain anticancer drugs, (ii) evaluate the fraction of renal clearance for pertinent anticancer drugs, and (iii) make general recommendations for the dosing of these drugs in the presence of impaired renal function. Pharmacokinetic, pharmacodynamic, and clinical toxicity information was obtained from current scientific and clinical literature. Recommendations for dosage adjustment of drugs is based on their nephrotoxicity, or renal clearance equal to or exceeding 30% of the administered dose. The specific formula used to calculate dosage adjustment of renally cleared anticancer drugs is based on fundamental pharmacokinetic principles. In addition, prospectively validated formulae for the dosage adjustment of specific agents, such as carboplatin are also reviewed. Forty-eight anticancer drugs are reviewed in this report. Nephrotoxicity is associated with 12 of these agents (Table 1). Renal clearance equal to or exceeding 30% of the administered dose is a characteristic of 17 of the drugs studied (Table 2), and a general recommendation for dose adjustment of these anticancer drugs is presented in Table 3. Renal clearance that is less than 30% of the administered dose is a feature of 31 anticancer drugs (Table 4) included in this review. This report provides general guidelines to adjust doses of renally excreted or nephrotoxic anticancer drugs in patients who present with altered renal function.

Antineoplastic Agents↗
PubMed1995

Low itraconazole serum concentrations following administration of itraconazole suspension to critically ill allogeneic bone marrow transplant recipients.

OBJECTIVE: To report itraconazole serum concentrations following administration of itraconazole suspension via orogastric feeding tubes to 2 critically ill allogeneic bone marrow transplant recipients. CASE SUMMARIES: A 38-year-old man and a 29-year-old man, each allogeneic bone marrow transplant recipients, were treated with oral itraconazole for documented fungal infections. Intubation and mechanical ventilation impeded ingestion of itraconazole capsules. Itraconazole was prepared initially as a suspension in intravenous lipid emulsion 20% and later as a suspension in citric acid 1.5% in D5W USP. Itraconazole serum concentrations were assayed using HPLC. Predose itraconazole serum concentrations were undetectable to 72 ng/mL. Postdose itraconazole serum concentrations were 5-97 ng/mL. Itraconazole concentrations measured in these patients were markedly lower than serum concentrations reported in the literature for similar doses administered to fed subjects. DISCUSSION: Efficacy of this antifungal agent is limited currently by the patient's ability to ingest and absorb the itraconazole capsules. Pathophysiologic factors and suspension formulation issues that likely contributed to decreased itraconazole absorption are discussed. CONCLUSIONS: Preparation and administration of itraconazole as a suspension did not enhance drug absorption in these patients. Furthermore, efficacy of itraconazole suspension may be affected by physical compatibility and chemical stability of the extemporaneous preparations.

Adult↗
PubMed1994

Otic administration of amphotericin B 0.25% in sterile water.

OBJECTIVE: To report otic administration of parenteral amphotericin B 0.25% in sterile water. CASE SUMMARY: A 44-year-old HIV+ man was diagnosed with otitis externa. The patient's past medical history was remarkable for positive Coccidioides immitis serology for more than five months, essential hypertension, and Barrett's esophagitis. Culture results from an ear swab revealed 4+ Aspergillus fumigatus and 3+ Staphylococcus, coagulase negative. Antiinfective therapy for the otitis externa included oral and topical antibacterial and antifungal medications. Amphotericin B 0.25% in sterile water was prepared by the pharmacy for topical otic administration. The otic amphotericin B was dispensed with instructions to refrigerate and assigned a one-week expiration date. The prescription called for instillation of 1-2 drops in each ear three times a day. The patient's signs and symptoms of otitis externa resolved during several weeks of antiinfective therapy. Topical administration of amphotericin B 0.25% in sterile water was not associated with any local adverse effects in this patient. DISCUSSION: The rationale for use of the parenteral amphotericin B formulation to prepare an otic dosage form, and the rationale for the specific concentration and expiration date chosen are discussed. CONCLUSIONS: This patient tolerated topical otic administration of amphotericin B 0.25% in sterile water when administered three times daily.

Administration, Topical↗
PubMed1992

Practical guidelines for preparing and administering amphotericin B.

Current practices used in the preparation and administration of amphotericin B are evaluated, and updated guidelines are presented. Intravenous admixtures of amphotericin B 0.25 and 1.4 mg/mL in 5% dextrose injection have an expiration date of 35 days and 36 hours, respectively. Since commercial formulations of amphotericin B lack a bacteriostatic agent, admixtures should be stored at 4-8 degrees C. Protection from fluorescent light is unnecessary. Admixtures may be prepared in polyolefin, glass, or polyvinyl chloride intravenous containers; certain evacuated intravenous containers contain buffers that can cause precipitation of amphotericin B. The addition of a buffering agent to the intravenous admixture is unnecessary when the initial pH of the 5% dextrose injection exceeds 4.2. The usual daily maintenance dose of amphotericin B is 0.5-1 mg/kg i.v. The manufacturer recommends beginning intravenous therapy with a 1-mg test dose. The initiation of therapy with incrementally increased doses may be detrimental if it delays the delivery of a therapeutic dose. Amphotericin B can be infused over one to two hours (less than or equal to 50 mg/hr) in patients with adequate renal function. Bladder instillation of amphotericin B 50 mg in 1 L of sterile water has been used to treat fungal cystitis. Ancillary medications administered to treat infusion-related adverse events should be used as prophylaxis in patients with a history of hypersensitivity or unacceptable reactions and as needed for relief of symptoms. Sodium supplementation should be implemented cautiously, on a patient-specific basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗
PubMed1991

Stability of amphotericin B in 5% dextrose injection at concentrations used for administration through a central venous line.

The stability of amphotericin B in 5% dextrose injection was studied at concentrations used for administration through a central venous line. Amphotericin B 60, 80, and 100 mg was diluted in 50 mL of 5% dextrose injection; final mean +/- S.D. concentrations after adjustment for total volume were 0.92 +/- 0.01, 1.20 +/- 0.03, and 1.40 +/- 0.03 mg/mL, respectively. For each concentration, six admixtures were prepared; of these, three were stored at 25 degrees C and three at 6 degrees C. Amphotericin B concentration was tested at 0, 4, 12, 24, and 36 hours by stability-indicating high-performance liquid chromatography. The admixtures were inspected visually at each time point for precipitation, turbidity, gas formation, and color change, and the pH was measured. Concentrations of amphotericin B remained within 3% of initial concentrations at each time point at both storage temperatures. No precipitation, turbidity, gas formation, or color change was observed, and no changes in pH were measured. Amphotericin B in 5% dextrose injection was stable at concentrations of 0.92, 1.20, and 1.40 mg/mL when stored at 6 and 25 degrees C for up to 36 hours.

Amphotericin B↗
PubMed1991

Recombinant interleukin-2: a biological response modifier.

The chemical properties, pharmacology, immunology, pharmacokinetics, clinical trials, adverse effects, and dosage and administration of recombinant interleukin-2 are reviewed. Recombinant interleukin-2 is an immunomodulating agent that stimulates the proliferation, activation, and differentiation of T and B cells, natural killer cells, and thymocytes. Two recombinant interleukin-2 products, aldesleukin and teceleukin, have been extensively studied. Most clinical experience with recombinant interleukin-2 has involved the treatment of renal cell carcinoma, melanoma, and colorectal cancer with a National Cancer Institute protocol. Patients with renal cell cancer and melanoma, who historically respond poorly to conventional therapy, have responded to therapy with recombinant interleukin-2. Recombinant interleukin-2 has been administered alone and in combination with lymphokine-activated killer cells, tumor-infiltrating lymphocytes, and interferons alfa and beta. In addition, the effect of dosage, administration rate, dosage schedule, route of administration, and cyclophosphamide pretreatment have been investigated. The adverse effects of recombinant interleukin-2 are generally reversible but are frequently severe and dose-related. Dose-limiting adverse effects include hypotension, edema, and renal dysfunction. Since hemodynamic monitoring and supportive care are essential, recombinant interleukin-2 should be administered in a critical-care setting by trained personnel. Recombinant interleukin-2 represents an advance in the therapy of renal cell cancer and melanoma and offers a new approach to the treatment of other refractory or recurrent malignancies.

Cell Division↗