PubMed Health⌕ Search

Biomedical subjects

P M Rainey

Publications and source records attributed to P M Rainey.

At least 19 recordsLinked to original sources
PubMed1998

Strategies for physician education in therapeutic drug monitoring.

Although therapeutic drug monitoring (TDM) is probably very useful overall, studies suggest that it could be used better. Many drug concentrations appear to have inappropriate indications or suboptimal timing, particularly in the inpatient setting. Undermonitoring is also a concern. Thus, it may be possible to both improve the quality of TDM and reduce the overall costs of care. Here we review approaches for improving the use of TDM and present some illustrative experiences. Specific approaches discussed include use of traditional approaches such as lectures and newsletters, multidisciplinary quality improvement efforts, formal TDM services, and use of the computer as a tool for education and behavior change. Computerized methods appear to hold substantial potential, particularly as more organizations develop better information systems, but other approaches are also effective and are complementary. To be most successful, interventions should consider all stages of the process.

Canada↗
PubMed1996

Rapid high-performance liquid chromatographic assay for atovaquone.

A rapid high-performance liquid chromatography assay has been developed for the drug atovaquone, which is currently being used to treat Pneumocystis carinii pneumonia and Toxoplasma gondii encephalitis associated with the acquired immunodeficiency syndrome (AIDS). Protein is precipitated from plasma with acetonitrile-aqueous 1% acetic acid (85:15). The supernatant is assayed on a C6 column using methanol-10 mM triethylamine in aqueous 0.2% trifluoroacetic acid (76:24) with detection at 254 nm. The working assay range was 0.5 to 50 micrograms/ml. Recovery was 97% and the between-day coefficients of variation were 2.1% at 50 micrograms/ml and 10.3% at 1 microgram/ml. A number of drugs commonly used to treat AIDS and its complications did not interfere with the assay.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii.

Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102). Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose. Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 micrograms.h/ml; halflife, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection. Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pentavalent antimony-mannan conjugate therapy of experimental visceral leishmaniasis.

Pentavalent antimony-mannan (Sb[V]-mannan) was 10-fold more potent than sodium stibogluconate in a murine model of visceral leishmaniasis. Liver antimony concentrations were six-fold higher after Sb[V]-mannan therapy compared with a dose of sodium stibogluconate that was equipotent in reducing liver parasite burdens. Murine toxicity of Sb[V]-mannan was variable, with a 50% lethal dose (LD50) for one preparation that was well above the concentration that killed 90% of the parasites, and for another preparation was only modestly higher than the concentration that killed 90% of the parasites.

Animals↗
PubMed1996

Metabolite and matrix interference in phenytoin immunoassays.

The major phenytoin metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin glucuronide (HPPG), was primarily responsible for the positive bias noted when uremic specimens were assayed with the Abbott TDx Free Phenytoin fluorescence polarization immunoassay. The amount of bias depended on both HPPG and phenytoin concentration, increasing with increases in either concentration. The new Abbott TDx II assays for phenytoin and free phenytoin exhibited no significant cross-reactivity with HPPG and no bias in clinical specimens from uremic patients. Both assays correlated well with Emit-based assays (r >0.98), had CVs of <3.5%, and had minimum detection limits of <0.1 mg/L. Calibration curves were stable for at least 6 weeks. All of the TDx assays cross-reacted with another metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), but expected HPPH concentrations are too low to cause a clinically significant bias. The Emit-based phenytoin assay exhibited a significant matrix effect when calibrators were prepared in defibrinated plasma processed to resemble serum.

Calibration↗
PubMed1995

Screening for lead poisoning by fingerstick in suburban pediatric practices.

OBJECTIVE: To assess the false-positive rate of blood lead determinations on samples obtained by fingerstick from children screened in private suburban and rural practices. METHODS: Screening capillary lead samples were obtained by fingerstick; children with capillary lead levels of 0.7 mumol/L (15 micrograms/dL) or greater were recalled for a confirmatory venous lead test that served as the criterion standard. Parents completed a five-question risk assessment questionnaire at the time of initial screening. SETTING: Four private suburban to rural practices that serve predominantly white, middle-class populations. PARTICIPANTS: Children seen for routine care between August 1992 and February 1993 (N = 1085; 98% between 6 months and 6 years of age). RESULTS: Capillary lead level was 0.7 mumol/L (15 micrograms/dL) or greater in 35 children (3% of total sample); venous lead samples were obtained in 30 patients. Nine of the elevated capillary lead results were true-positives (venous lead = 0.7, 0.8, 0.8, 0.9, 0.9, 0.9, 1.1, 1.1, and 1.7 mumol/L [15, 17, 17, 18, 18, 18, 22, 22, and 35 micrograms/dL]); parents of only two of these children answered yes to any question on the risk assessment questionnaire. Although the false-positive rate of the capillary lead screening test was 70% (21/30) in this setting, only 2% of the total sample had a false-positive screening test (an average of fewer than one false-positive per month per practice). Screening by fingerstick allowed phlebotomy to be avoided for 97% of the children. CONCLUSION: Fingerstick screening for lead poisoning is a reasonable alternative to direct venous testing within private suburban and rural practices, provided that care is taken to avoid specimen contamination, that appropriate caution is used in the interpretation of screening test results, and that medical and environmental interventions are based on the results of confirmatory venous testing.

Blood Specimen Collection↗
PubMed1995

Identification of patients for pharmacologic review by computer analysis of clinical laboratory drug concentration data.

Clinical pharmacokinetics evaluation and consultation can improve drug therapy and decrease the incidence of adverse reactions in selected patients. However, identification of patients appropriate for review is difficult. The authors developed a microcomputer-based expert system that scans clinical laboratory drug concentration data to identify patients for follow-up. Rules were developed from a review of data for digoxin, phenytoin, and theophylline. These were implemented in software that provides for simple rule creation and modification, on-screen graphic review of data, and printing of chart reports. This program is readily adapted for use with most laboratory information systems. In a retrospective study of 868 patients monitored for digoxin, phenytoin, and theophylline, 29% were flagged as having drug level profiles of possible concern. The majority (62%) of these patients had multiple specimens flagged, suggesting persistent problems. These data suggest that patients can be identified for follow-up by scanning serial drug concentrations, allowing consultative resources to be focused on patients most likely to benefit from them.

Clinical Laboratory Information Systems↗
PubMed1995

Pyrimethamine analysis by enzyme inhibition and HPLC assays.

Pyrimethamine is an antiparasitic agent currently used for therapy of central nervous system toxoplasmosis, a disease seen with increasing frequency in association with the AIDS epidemic. Monitoring of pyrimethamine levels may be particularly important because patients may be treated with high doses of the drug for extended periods of time. The authors have developed and validated both a new enzyme inhibition assay that can be run on an automated analyzer and an improved high performance liquid chromatography (HPLC) method. The calibration range of both methods is 100 to 3,000 micrograms/L. Both demonstrate good linearity, specificity, and precision, and correlate well with one another (r = 0.99). The CVs of the enzyme inhibition assay were < or = 8.6% and those of the HPLC method were < or = 5.4%. No interference was noted for a variety of drugs likely to be used concomitantly with or in lieu of pyrimethamine with the exception of a minor interference from trimethoprim in the enzyme inhibition assay. The major advantage of the enzyme inhibition assay is its ease of automation. The major advantages of the HPLC assay are its precision and relative simplicity. These methods should facilitate therapeutic monitoring of pyrimethamine.

Calibration↗
PubMed1995

In vitro antileishmanial properties of tri- and pentavalent antimonial preparations.

To better understand the antileishmanial effects of antimonial agents we synthesized complexes of tri- and pentavalent antimony with mannan. The 50% inhibitory concentrations (IC50s) of these agents, along with those of potassium antimony tartrate [Sb(III)] and sodium stibogluconate [Sb(V)], were determined for promastigotes and intramacrophage amastigotes. The trivalent antimonial agents were more potent than the pentavalent agents. Although the IC50s were 60- to more-than-600-fold higher for promastigotes than for amastigotes, similar intracellular antimony concentrations in both life forms were measured after incubation with all four drugs at their respective IC50s. Macrophages accumulated antimony during a 4-h exposure that was retained intracellularly for at least 3 days. Amastigotes inside macrophages had a higher antimony content 6 days after a single 4-h treatment than they did immediately after treatment, suggesting that macrophages serve as a reservoir for antimonial agents and prolong parasite exposure. Macrophages concentrated antimony from the medium with potassium antimony tartrate, trivalent antimony-mannan, and pentavalent antimony-mannan treatments. N-Acetylcysteine antagonized the antileishmanial effects of these three drugs against intracellular amastigotes; in contrast, it had minimal effects on the action of sodium stibogluconate.

Acetylcysteine↗
PubMed1994

Screening for lead poisoning in an urban pediatric clinic using samples obtained by fingerstick.

OBJECTIVE: To assess the false positive rate of blood lead (BPb) determinations on samples obtained by fingerstick from children screened in an urban clinic. METHOD: From a single fingerstick (N = 1573), blood was collected in a capillary tube for determining lead concentration (CPb) by graphite furnace and an additional sample was absorbed onto a filter paper for determining lead concentration (FPb) by atomic absorption spectrophotometry with Delves cup. Zinc protoporphyrin (ZPP) was measured immediately and a confirmatory venous lead (VPb) specimen was obtained at the same visit if the ZPP was > or = 35 micrograms/dL (0.6 mumol/L); children with either a CPb or FPb > or = 15 micrograms/dL (0.7 mumol/L) were later recalled for determining VPb. RESULTS: For the 172 children who had a VPb on the same day as the screening tests, the false positive rates (95% confidence intervals) at a lead threshold of 15 micrograms/dL (0.7 mumol/L) were: CPb, 13.5% (6.7-20.3); FPb, 19.1% (11.8-26.4). Analyses using all 679 screens with a paired venous specimen (mean delay between screen and venous testing = 30 days) yielded much higher false positive rates (CPb, 31.3%; FPb, 46.0%). CONCLUSIONS: Screening for lead poisoning is feasible within an urban pediatric clinic by direct measurement of lead concentration in blood samples obtained by fingerstick. The false positive rate that can be obtained is acceptable given the precision of measuring BPb concentration. Practitioners using a staged screening protocol may incorrectly attribute a higher false positive rate to the screening tests, when much of the error may be due to the temporal variability of BPb resulting from both biologic variability in BPb concentration and intermittent exposures.

Child↗
PubMed1994

Solid-phase extraction combined with radioimmunoassay for measurement of zalcitabine (2',3'-dideoxycytidine) in plasma and serum.

Of the antiviral agents that are currently in clinical use in the US for therapy for human immunodeficiency virus infections, zalcitabine (ddC) is the most potent and is effective at the lowest plasma concentrations. The two reported procedures for measuring these low concentrations involve a chromatographic technique coupled with mass spectrometry. We have developed a procedure combining solid-phase extraction with a strong cation-exchange resin and commercially available RIA reagents for the quantification of ddC in plasma or serum. The method demonstrates good linearity, specificity, and precision, with overall CVs of < 10% from 2-20 micrograms/L and 17% at 0.8 microgram/L (the lower limit of quantitation). No significant cross-reactivity with nucleoside analogs other than ddC analogs was noted. The major advantages of this assay are its efficiency and relative simplicity, which should facilitate its performance in many laboratories.

Antiviral Agents↗
PubMed1993

Antimony quantification in Leishmania by electrothermal atomic absorption spectroscopy.

Tri- and pentavalent antimony were quantified in Leishmania mexicana pifanoi amastigotes and promastigotes by atomic absorption spectroscopy with electrothermal atomization. Leishmania grown in axenic culture were treated with either potassium antimony tartrate [Sb(III)] or sodium stibogluconate [Sb(V)]. The parasites were collected, digested with nitric acid, and subjected to atomic absorption spectroscopy. The method was linear from 0 to 7 ng of antimony. The interassay coefficients of variation were 9.6 and 5.7% (N = 5) for 0.52 and 3.7-ng samples of leishmanial antimony, respectively. The limit of detection was 95 pg of antimony. The assay was used to characterize Sb(III) and Sb(V) influx and efflux kinetics. Influx rates were determined at antimony concentrations that produced a 50% inhibition of growth (IC50). The influx rates of Sb(V) into amastigotes and promastigotes were 4.8 and 12 pg/million cells/h, respectively, at 200 micrograms antimony/ml. The influx rate of Sb(III) into amastigotes was 41 pg/million cells/h at 20 micrograms antimony/ml. Influx of Sb(III) into promastigotes at 1 microgram antimony/ml was rapid and reached a plateau of 175 pg/million cells in 2 h. Efflux of Sb(III) and Sb(V) from amastigotes and promastigotes exhibited biphasic kinetics. The initial (alpha) half-life of Sb(V) efflux was less than 4 min and that of Sb(III) was 1-2 h. The apparent terminal (beta) half-lives ranged from 7 to 14 h.

Animals↗