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Biomedical subjects

D W Grabe

Publications and source records attributed to D W Grabe.

10 recordsLinked to original sources
PubMed2001

Cefazolin dialytic clearance by high-efficiency and high-flux hemodialyzers.

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Adult↗
PubMed1999

Pharmacokinetics of intermittent intraperitoneal ceftazidime.

Ceftazidime is currently recommended as an alternative first-line agent in the treatment of peritonitis and for Pseudomonas peritonitis. The pharmacokinetics of intermittent intraperitoneal (i.p.) ceftazidime have been poorly characterized. This study was designed to characterize the pharmacokinetic disposition of a single dose of ceftazidime in anuric and non-anuric CAPD patients, over 48 hours. This was a prospective, open label, pharmacokinetic study. The study was conducted in an independent, outpatient dialysis center. Ten volunteer continuous ambulatory peritoneal dialysis (CAPD) patients with and without residual renal function, no peritonitis or antibiotics in the previous 4 weeks, and on CAPD for at least 2 months were recruited. Patients received a single dose of i.p. ceftazidime (15 mg/kg) in the first daytime exchange over a 6-hour dwell, after an overnight dwell. Serum, urine, and dialysate were collected over a 48-hour period. A high-pressure liquid chromatography (HPLC) assay was used to analyze ceftazidime in these samples. Pharmacokinetic parameters were calculated. Six of the 10 patients were non-anuric with a mean residual renal creatinine clearance of 2.9 +/- 1.6 mL/min. The mean +/- SD bioavailability was 72% +/- 14%, and the volume of distribution was 0.34 +/- 0.08 L/kg. The mean serum elimination half-life of 22 +/- 5 hours. The peritoneal clearance was 5.74 +/- 1.6 mL/min. No difference was detected between anuric and nonanuric patients. Mean plasma and dialysate concentrations at 24 hours were 24 +/- 6 microg/mL and 18 +/- 7 microg/mL, respectively, and were 12.0 +/- 3.6 microg/mL and 7.4 +/- 3.1 microg/mL at 48 hours, respectively. Once-daily i.p. dosing of ceftazidime achieves serum and dialysate levels greater than the MIC of sensitive organisms over 48 hours.

Adult↗
PubMed1999

Indinavir-induced nephropathy.

We report the case of a 38-year-old male who developed renal insufficiency while on the protease inhibitor, indinavir. This patient had an increase in serum creatinine over a period of approximately one year, along with persistently abnormal urinalysis. A renal biopsy was performed and showed marked tubular crystal deposition. The indinavir was discontinued, and after two months the patient's serum creatinine and urinalysis returned to normal. To our knowledge this is the second case of indinavir associated nephropathy.

Adult↗
PubMed1998

Development of an immunoassay for monitoring the levels of ciprofloxacin in patient samples.

It has been traditional to measure drug concentrations using high pressure liquid chromatography (HPLC). While this method is highly accurate, it is time consuming and requires the use of appropriate standards for identification of the compound. In addition, identification and quantification of drugs from patient samples requires significant manipulation to remove protein. In contrast, enzyme-linked immunoassays (EIA) are able to assay samples with a high degree of specificity, and are able to process multiple samples at a time. In addition, serum proteins do not interfere with sample quantification and samples may be tested without significant preparation. We describe the development of an EIA for the detection of ciprofloxacin in serum and dialysate samples. The immunoassay is specific for ciprofloxacin and is sensitive for picogram amounts of the antibiotic.

Animals↗
PubMed1998

Chromium picolinate toxicity.

OBJECTIVE: To describe a case of toxicity secondary to chronic ingestion of 6-12 times the recommended daily allowance of over-the-counter (OTC) chromium picolinate. CASE SUMMARY: A 33-year-old white woman presented with weight loss, anemia, thrombocytopenia, hemolysis, liver dysfunction (aminotransferase enzymes 15-20 times normal, total bilirubin 3 times normal), and renal failure (serum creatinine 5.3 mg/dL; blood urea nitrogen 152 mg/dL). She had ingested chromium picolinate 1200-2400 microg/d for the previous 4-5 months to enhance weight loss. The patient had chromium plasma concentrations 2-3 times normal. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome were ruled out by clinical findings, peripheral blood smears, and a bone marrow biopsy. The patient was managed with supportive measures and received blood product transfusions and hemodialysis. Hemolysis stabilized and liver function improved over 6 days. Liver function returned to normal prior to discharge. Renal function began to return on day 12 and her serum creatinine on discharge was 1.3 mg/dL. One year later, all laboratory values were within normal limits. DISCUSSION: Trivalent chromium is an essential trace element that is considered safe when ingested in normal quantities. Trivalent chromium compounds are used by patients to enhance weight loss, increase lean body mass, and/or improve glycemic control. Information regarding the toxicity of chromium picolinate is limited. CONCLUSIONS: Chromium supplements may cause serious renal impairment when ingested in excess. Medication histories should include attention to the use of OTC nutritional supplements often regarded as harmless by the public and lay media.

Acute Kidney Injury↗
PubMed1997

Evaluation of drug-related problems in an outpatient hemodialysis unit and the impact of a clinical pharmacist.

PURPOSE: Drug-related morbidity and mortality are significant problems in the U.S. Recognition and resolution of drug-related problems (DRP) will decrease drug-related morbidity and mortality and promote optimal therapeutic outcomes. It was the objective of this study to identify DRP in hemodialysis outpatients by performing medication reviews; make appropriate recommendations and determine the significance of any interventions; and estimate outcome in terms of any changes in number of medications/patient or doses/day. METHODS: A thorough medication review was conducted with each patient after review of the computerized medication profiles and medical records. Each updated profile was assessed by a clinical pharmacist for the presence of any of the 8 classical DRP plus 2 additional categories (therapeutic duplication and other [specific for dialysis e.g., dry weight]). Appropriate recommendations were made to the physician. Accepted recommendations were deemed as interventions and assigned a significance rank on a published scale of 1 (adverse significance) to 6 (extremely significant) by each of the investigators. A final rank was assigned upon agreement between investigators. Changes in numbers of doses/day or medications/patient were determined. RESULTS: 49 patients were reviewed and 45 patients (21 women, 24 men) were included in the final analysis. Over one month 126 DRP were identified and 102 interventions were made. Drug interactions constituted the most common DRP (27.5%). The second most common DRP (26.5%) was in the dialysis-specific group. The number of interventions per significance rank were as follows: rank 1:0 (0%); rank 2: 7 (6.9%); rank 4: 80 (78%); rank 5: 5 (4.9%); rank 6: 1 (1%). Patients were taking a mean of 10.9 +/- 3.9 medications and a mean of 14.5 +/- 6 doses/day (range, 2-33) prior to the study and 10.7 +/- r and 14.4 +/- 5.8 by the end of the study period. CONCLUSIONS: With the addition of a clinical pharmacist in an hemodialysis unit numerous DRP were detected and interventions made. The majority of interventions were significant and possibly led to better therapeutic outcomes.

Drug Interactions↗