PubMed Health⌕ Search

Biomedical subjects

Kimberly L Napoli

Publications and source records attributed to Kimberly L Napoli.

7 recordsLinked to original sources
PubMed2006

Is microparticle enzyme-linked immunoassay (MEIA) reliable for use in tacrolimus TDM? Comparison of MEIA to liquid chromatography with mass spectrometric detection using longitudinal trough samples from transplant recipients.

In the larger transplant centers where technical expertise is available, liquid chromatography with mass spectrometric detection (LC-MS) for tacrolimus therapeutic drug monitoring is replacing the popular microparticle enzyme-linked immunoassay (MEIA) as a cost-effective alternative technology. As more labs convert to LC-MS, the accuracy, precision, selectivity, and sensitivity of the tacrolimus MEIA are being challenged, using data from large populations of clinical samples. However, little attention has been paid to how the results of particular procedures may differ within and among individual patients and to how such differences may relate to patients' characteristics or to relevant biochemical parameters. So, after validation of an LC/MS procedure and verification of an LC/MS/MS procedure, the author analyzed 552 serial trough blood tacrolimus samples, collected from 38 patients over a 3-month period, by controlled MEIA and LC-MS procedures. Corresponding hematocrit and serum albumin level data were obtained. In an attempt to investigate whether the observations of others who studied population-based data could be illustrated for individuals, longitudinal data from several patients were plotted to visually elucidate any relations between the tacrolimus concentration and biochemical data. Finally tacrolimus concentration, hematocrit, and serum albumin data were compared using data stratified by transplant type, in-/outpatient status, male/female gender, or period elapsed since transplant surgery. The validated/verified LC-MS procedures were shown to be much better controlled than the MEIA during the 3-month parallel comparison study period. The longitudinal data of several individuals who experienced wide changes in the biochemical parameters clearly illustrated the relation between the difference in tacrolimus concentrations determined by MEIA and LC-MS and hematocrit (and sometimes albumin). Differences between the MEIA- and LC-MS-determined tacrolimus concentration data were strongly correlated to transplant type, in-/outpatient status, gender, time elapsed since liver transplant surgery, hematocrit, and weakly to serum albumin levels. In summary, the LC-MS methods provide highly reliable and reproducible estimates of tacrolimus concentrations, whereas the performance of MEIA technology did not provide reliable long-term performance for longitudinal therapeutic drug monitoring of tacrolimus because it was effected by several inherent demographic factors and by factors that can change over time in transplant recipients.

Adult↗
PubMed2006

12-hour area under the curve cyclosporine concentrations determined by a validated liquid chromatography-mass spectrometry procedure compared with fluorescence polarization immunoassay reveals sirolimus effect on cyclosporine pharmacokinetics.

Liquid chromatographic (LC) procedures have been applied to cyclosporine therapeutic drug monitoring (TDM) since the agent was introduced in 1983. In recent years, the advance to mass spectrometric (MS) detection has enhanced the capability of LC by providing more sensitive and selective detection, a wider analytical range, faster turnaround time, and relative ease of use. Although fluorescence polarization immunoassay (FPIA) is a widely popular technology for cyclosporine TDM, it is compromised by a limited analytical range and lack of selectivity for parent drug. Here, we present the validation of an LC-MS procedure that is equally applicable to use on single or tandem quadrupole instruments. An extensive method comparison with FPIA was performed using samples (n = 726) collected for full 12-hour pharmacokinetic studies on 121 renal transplant recipients. Patients were receiving either full-dose cyclosporine or primary sirolimus therapy complimented with low-dose cyclosporine. FPIA overestimated all cyclosporine concentrations to varying degrees depending on hour of collection (12 approximately 0 > 8 > 6 > 4 > 2-hour). The mean FPIA/LC-MS ratio was significantly higher at 0 hour in the presence of sirolimus (P = 0.008) and trended higher at the other collection times and for area under the curve. Sirolimus also had a significant effect on the FPIA/LC-MS ratio at 12 hour in studies with tmax at 2 hours (P = 0.042) but not 4 hours (P = 0.735). Use of LC-MS procedures for cyclosporine TDM provides for quantitation of approximately 20% more samples from patients receiving low-dose cyclosporine and reduces any errors in dosing that may occur because of the sirolimus effect on cyclosporine pharmacokinetics when combined with varying degrees of overestimation of cyclosporine concentrations by FPIA.

Area Under Curve↗
PubMed2005

Validation of a practical liquid chomatography with ultraviolet detection method for quantification of whole-blood everolimus in a clinical TDM laboratory.

Until now, only LC/MS methods for quantification of everolimus have been published. The authors validated an LC/UV method for quantification of everolimus from whole blood. The authors sought to improve on the protocol for sirolimus determination previously reported by French et al. Everolimus and the internal standard 32-desmethoxy-rapamycin were extracted from whole blood with n-butyl chloride after precipitation of proteins and then reconstituted in mobile phase and washed with hexane to remove lipids. Everolimus was quantified by reverse-phase chromatography of the extraction product at 60 degrees C, using an isocratic 60% acetonitrile/water mobile phase at a flow rate of 1.0 mL/min. Everolimus eluted at approximately 9.6 minutes, and internal standard at approximately 11.6 minutes. A series of 32 calibration curves were linear over the concentration range of 2-100 ng/mL using 0.5 mL of whole blood per sample with r > 0.990 and slope displaying an 8.8 interassay %CV. At the lower limit of quantification, 2 ng/mL, the percentage bias and %CV were -5.0% and 14.7%, respectively. Intraassay precision at weighed-in levels of 6, 12, and 32 ng/mL were 2.4% to 6.4%, and biases were -10.7% to -8.5%. These same quality control materials yielded -6.3% to -0.8% biases from the expected values and 2.4% to 10.9% interday precision, respectively. This method for everolimus determination, validated according to FDA guidelines, provides longer column life and better sensitivity than that of French et al for sirolimus determination. This protocol also provides acceptable accuracy and precision over the expected therapeutic range and allows 1 technologist using 1 LC/UV system to run up to 5000 samples per year with confidence.

Chromatography, Liquid↗
PubMed2004

Analytic aspects of cyclosporine monitoring, on behalf of the IFCC/IATDMCT Joint Working Group.

The use of therapeutic drug monitoring strategies for cyclosporin (CsA) has evolved markedly in recent years since previous consensus guidelines were presented. Apart from the introduction of some new methods, the major change has been the shift away from the traditional predose/trough (C0) sample. The most popular alternative has been shown to be a 2-hour postdose (C2) sample. This has presented a challenge to clinical laboratories where typical C2 sample concentrations exceed the upper limit of the calibration range for their chosen CsA method, hence requiring an accurate dilution to be performed. Data from the Australian/New Zealand survey, as well as that in the International CsA Proficiency Testing Program, have demonstrated both a plethora of dilution protocols and resultant widespread failure of many laboratories to obtain accurate results. This paper compares data from several independent sources, pointing to international problems for reliable CsA measurement in clinical laboratories. This includes the CsA method selection criteria adopted by a large percentage of laboratories in various surveys, indicating that the least specific mFPIA methods have been widely adopted.

Australia↗
PubMed2002

International Federation of Clinical Chemistry/International Association of Therapeutic Drug Monitoring and Clinical Toxicology working group on immunosuppressive drug monitoring.

Issues surrounding the measurement and interpretation of immunosuppressive drug concentrations have been summarized in a number of consensus documents. The Scientific Division of the International Federation of Clinical Chemistry has formed a working group in collaboration with the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. This paper sets out the goals of the working group in light of the developments that have occurred in the field of immunosuppressive drug monitoring since the publication of the last consensus documents.

Animals↗
PubMed2001

Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations.

This study correlated the dynamic effects of sirolimus (rapamycin; RAPA) and cyclosporine (CsA) alone versus in combination to produce renal dysfunction, myelosuppression, or hyperlipidemia, with their corresponding blood and tissue concentrations. After salt-depleted rats were treated with RAPA (0.4 to 6.4 mg/kg per d) and/or CsA (2.5 to 20.0 mg/kg per d) for 14 d, the GFR, lipid levels, bone marrow cellularity, and CsA/RAPA concentrations in whole blood versus liver or renal tissues were measured, and the median effect model was used to discern the type of drug interactions. Compared with vehicle controls (1.98 +/- 0.34 ml/min), GFR values were reduced only by large doses of drug monotherapy, namely RAPA (3.2 mg/kg per d = 1.2 +/- 0.02 ml/min or 6.4 mg/kg per d = 1.3 +/- 0.2 ml/min; both P < 0.01) or CsA (10.0 mg/kg per d = 1.2 +/- 0.1 ml/min or 20.0 mg/kg per d = 0.8 +/- 0.4 ml/min; both P < 0.01). In contrast, hosts that were treated with smaller doses of CsA/RAPA combinations showed more pronounced effects in reduction of GFR values: 2.5/0.4 mg/kg per d, modestly (1.5 +/- 0.5 ml/min; P < 0.01); 5.0/0.8 mg/kg per d, moderately (0.23 +/- 0.01 ml/min; P < 0.001); and higher-dose groups, markedly. The exacerbation of renal dysfunction seemed to be due to a pharmacokinetic interaction of RAPA to greatly increase CsA concentrations in whole blood and, particularly, in kidney tissue. In contrast, the pharmacodynamic effects of CsA to potentiate two RAPA-mediated toxicities-myelosuppression and increased serum cholesterol/low-density lipoprotein cholesterol-occurred independently of pharmacokinetic interactions. RAPA aggravates CsA-induced renal dysfunction owing to a pharmacokinetic interaction, whereas CsA produces a pharmacodynamic effect that augments RAPA-induced myelosuppression and hyperlipidemia.

Animals↗