Search PubMed⌕ Search

Biomedical subjects

P M Rainey

Publications and source records attributed to P M Rainey.

At least 19 recordsLinked to original sources
PubMed2001

Effect of opioid dependence pharmacotherapies on zidovudine disposition.

Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in 52 subjects receiving the opioid dependence pharmacotherapies l-alpha-acetylmethadol LAAM, buprenorphine, or naltrexone, and 17 non-opioid-treated controls. Relative to the area under the time-concentration curve (AUC) of ZDV in control subjects, no statistically significant differences in ZDV AUC were observed in participants treated with LAAM (p = .75), buprenorphine (p = .37), or naltrexone (p = .34). While methadone maintenance may result in ZDV toxicity and possibly require dose adjustments, other opioid pharmacotherapies should not produce ZDV toxicity.

Anti-HIV Agents↗
PubMed2000

Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure.

We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Cue-dose training with monetary reinforcement: pilot study of an antiretroviral adherence intervention.

OBJECTIVE: To assess the feasibility and efficacy of two interventions for improving adherence to antiretroviral therapy regimens in HIV-infected subjects compared with a control intervention. DESIGN: Randomized, controlled, pilot study. SETTING: Department of Veterans Affairs HIV clinic and community-based HIV clinical trials site. PARTICIPANTS: Fifty-five HIV-infected subjects on stable antiretroviral therapy regimens. Subjects were predominantly male (89%) and African American (69%), and had histories of heroin or cocaine use (80%). INTERVENTIONS: Four weekly sessions of either nondirective inquiries about adherence (control group, C), cue-dose training, which consisted of the use of personalized cues for remembering particular dose times, and feedback about medication taking using Medication Event Monitoring System (MEMS) pill bottle caps, which record time of bottle opening (CD group), or cue-dose training combined with cash reinforcement for correctly timed bottle opening (CD+CR). MEASUREMENTS: Opening of the pill bottle within 2 hours before or after a predetermined time was measured by MEMS. RESULTS: Adherence to the medication as documented by MEMS was significantly enhanced during the 4-week training period in the CD+CR group, but not in the CD group, compared with the control group. Improvement was also seen in adherence to antiretroviral drugs that were not the object of training and reinforcement. Eight weeks after training and reinforcement were discontinued, adherence in the cash-reinforced group returned to near-baseline levels. CONCLUSIONS: Cue-dose training with cash reinforcement led to transient improvement in adherence to antiretroviral therapy in a population including mostly African Americans and subjects with histories of drug abuse. However, we were not able to detect any sustained improvement beyond the active training period, and questions concerning the timing and duration of such an intervention require further study. Randomized, controlled clinical studies with objective measures of adherence can be conducted in HIV-infected subjects and should be employed for further evaluation of this and other adherence interventions.

Anti-HIV Agents↗
PubMed1999

Management of a Sabiá virus-infected patients in a US hospital.

OBJECTIVE: To describe the hospital precautions used to isolate a Sabiá virus (arenavirus: Arenaviridae)-infected patient in a US hospital and to protect hospital staff and visitors. DESIGN: Investigation of a single case of arenavirus laboratory-acquired infection and associated case-contacts. SETTING: A 900-bed, tertiary-care, university-affiliated medical center. PATIENTS OR OTHER PARTICIPANTS: The case-patient became ill with Sabiá virus infection. The case-contacts consisted of healthcare workers, coworkers, friends, and relatives of the case-patient. INTERVENTION: Enhanced isolation precautions for treatment of a viral hemorrhagic fever (VHF) patient were implemented in the clinical laboratory and patient-care setting to prevent nosocomial transmission. The enhanced precautions included preventing aerosol spread of the virus from the patient or his clinical specimens. All case-contacts were tested for Sabiá virus antibodies and monitored for signs and symptoms of early disease. RESULTS: No cases of secondary infection occurred among 142 case-contacts. CONCLUSIONS: With the frequency of worldwide travel, patients with VHF can be admitted to a local hospital at any time in the United States. The use of enhanced isolation precautions for VHF appeared to be effective in preventing secondary cases by limiting the number of contacts and promoting proper handling of laboratory specimens. Patients with VHF can be managed safely in a local hospital setting, provided that appropriate precautions are planned and implemented.

Accidents, Occupational↗
PubMed1999

Performance characteristics of three serum iron and total iron-binding capacity methods in acute iron overdose.

Accurate serum iron and total iron binding capacity (TIBC) measurements may be useful in acute iron overdoses. Two alumina column TIBC methods were found to measure increased TIBC when free iron was present. A homogeneous TIBC method gave consistent results until iron concentrations exceeded 500 micrograms/dL (90 mumol/L), when it began to underestimate the TIBC. Serious iron overdoses require chelation therapy with deferoxamine. Iron recovery was reduced by up to 50% for all 3 methods with clinically achievable concentrations of deferoxamine 8,400 micrograms/dL (150 mumol/L). TIBC measurements by both alumina column methods were reduced by deferoxamine in the presence of free iron and unaffected when the iron concentration was less than the TIBC. The homogeneous TIBC method yielded falsely elevated results in the presence of free deferoxamine. Procedures that measure TIBC by addition of excess ferric iron followed by alumina adsorption are not suitable for monitoring TIBC in acute iron overdose. The homogeneous TIBC assay can be used in acute iron overdose but underestimates TIBC when iron concentrations exceed 500 micrograms/dL (90 mumol/L). None of the methods examined are useful for measuring iron or TIBC in the presence of deferoxamine.

Acute Disease↗
PubMed1998

Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262).

Large numbers of injection drug users (IDUs) are infected with HIV and receive both methadone and zidovudine (ZDV) therapy. Pharmacokinetic interactions between these agents may effect drug efficacy, toxicity, and compliance. To confirm and expand previous studies that identified a potential interaction between ZDV and methadone, we performed a within-subject study to determine oral and intravenous ZDV pharmacokinetics in 8 recently detoxified, heroin-addicted patients with HIV disease before and after initiation of methadone treatment. Acute methadone treatment increased oral ZDV in the area under the curve (AUC) by 41% (p = .03) and intravenous ZDV AUC by 19% (p = .06). Clearance was reduced by 21% (p = .007) and 19% (p = .04), respectively. Chronic methadone treatment increased oral ZDV AUC by 29% (p = .15) and intravenous ZDV AUC by 41% (p = .05). Clearance was decreased by 26% for both routes (p = .02). Methadone levels remained in the therapeutic range during ZDV treatment. These effects resulted primarily from inhibition of ZDV glucuronidation, but also from decreased renal clearance of ZDV. This study confirms that methadone-maintained patients receiving standard ZDV doses experience greater ZDV exposure and may be at increased risk for ZDV side effects and toxicity. Increased toxicity surveillance and possibly reduction in ZDV dose are indicated when these two agents are given concomitantly.

Administration, Oral↗
PubMed1998

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens.

OBJECTIVE: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. METHODS: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl). RESULTS: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. CONCLUSION: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

Adult↗
PubMed1998

The effect of fluconazole on the clinical pharmacokinetics of methadone.

A randomized, double-blinded, placebo-controlled pharmacokinetic and safety trial was conducted to determine the effect of fluconazole on methadone disposition. Volunteers receiving methadone maintenance therapy were randomized to receive either 200 mg/day oral fluconazole (n = 13) or placebo (n = 12). After 14 days there was a 35% average increase in serum methadone area under the curve relative to baseline among patients receiving fluconazole (p = 0.0008). At the same time, mean serum methadone peak and trough concentrations increased by 27% (p = 0.0076) and 48% (p = 0.0023), respectively, and oral clearance of methadone was reduced by 24% (p = 0.0007). In contrast, the pharmacokinetics of methadone were unaltered in the placebo group. Renal clearance of methadone was not significantly affected by fluconazole or placebo therapy. Although exposed to increased concentrations of methadone, patients treated with fluconazole did not exhibit signs or symptoms of significant narcotic overdose.

Adult↗
PubMed1998

Characterization of the antimonial antileishmanial agent meglumine antimonate (glucantime).

Meglumine antimonate (Glucantime), a drug of choice for the treatment of leishmaniasis, is produced by the reaction of pentavalent antimony with N-methyl-D-glucamine, a carbohydrate derivative. We investigated the structure and composition of meglumine antimonate, which remain poorly understood, despite 50 years of use. Measurement of the antimony content of meglumine antimonate powder indicated a 1:1.37 molar ratio of antimony to N-methyl-D-glucamine. Osmolality measurements performed with meglumine antimonate solutions demonstrated an average of 1.43 antimony atoms per molecule of meglumine antimonate. The osmolality of a 1:10 dilution of stock meglumine antimonate increased by 45% over 8 days, suggesting hydrolysis to less complex species. A comparison of the proton nuclear magnetic resonance spectra of N-methyl-D-glucamine and meglumine antimonate revealed an increase in complexity in the latter but with all of the resonances of the former still being evident, consistent with the presence of coordination complexes between antimony and each of the N-methyl-D-glucamine hydroxyls. Fast atom bombardment and electrospray ionization mass spectrometry coupled with several derivatization procedures provided evidence that up to four N-methyl-D-glucamine hydroxyls are coordinated with each antimony. A series of oligomers were observed. The major moiety has a molecular mass of 507 atomic mass units and consists of NMG-Sb-NMG, where Sb represents antimony and NMG represents N-methyl-D-glucamine. Additional species containing up to four antimony atoms and five N-methyl-D-glucamine moieties and corresponding to the general form (NMG-Sb)n-NMG are also present. These results suggest that this agent is a complex mixture that exists in equilibrium in aqueous solution.

Antiprotozoal Agents↗
PubMed1998

A cluster of cases of severe cardiotoxicity among kala-azar patients treated with a high-osmolarity lot of sodium antimony gluconate.

In India, sodium antimony gluconate is the drug of choice for kala-azar. Due to increasing unresponsiveness to this drug in the current epidemic that began in the early 1970s, daily doses of 20 mg/kg/day for 30 days or more is recommended as opposed to the 10 mg/kg/day dose for 6-10 days used in the past. Of the 130-150 patients treated annually at our center with locally made sodium antimony gluconate, serious cardiotoxicity has occurred in less than 10%. During April 1995 at the University Hospital in Varanasi, we encountered life-threatening cardiotoxicity after 3-28 days of therapy in each of the eight patients being treated with a new lot of this drug made by a different manufacturer. Of the eight patients, six each developed congestive heart failure and/or prolongation of the corrected QT interval (QTc), and three died as a direct consequence of drug-induced toxicities. In three instances, the life-threatening complications occurred with a cumulative dose of less than 300 mg/kg. In patients with prolonged QTc, ventricular premature beats and ventricular tachycardia were recorded; in one patient, the ventricular tachycardia progressed to torsade de pointes, culminating in ventricular fibrillation and death. Since switching to different lots of this drug, we have not seen further clustering of dangerous cardiotoxicity. The antimony content of the implicated drug was comparable with that in lots from other manufacturers that did not show overt toxicity, but the osmolarity was approximately 300 mOsm/L higher. The simple technique of measuring of osmolarity may help identify inappropriately manufactured drug.

Adult↗
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↗