摘要:

Renal drug elimination involves three major processes: glomerular filtration, tubular secretion, and tubular reabsorption. Drug filtration is a simple unidirectional diffusion process. Renal tubular secretion and reabsorption are bidirectional processes that often involve both passive diffusion and carrier‐mediated membrane processes. Various in vivo and in vitro techniques are available to study renal drug elimination and renal drug transport. The complete renal handling of a drug is best understood from data obtained from a combination of in vivo and in vitro methodologies. At the membranes of the renal proximal tubule, a number of carrier systems are involved in the tubular secretion and/or reabsorption of various drugs. Organic acid and base transporters are two major carrier systems important in the tubular transport of a number of organic acid and base drugs, respectively. Nucleoside and P‐glycoprotein transporters appear to play an important role in renal tubular transport of dideoxynucleosides (e.g., zidovudine, dideoxyinosine) and digoxin, respectively. Clinically, these transporters are not only necessary for the renal tubular secretion and reabsorption of various drugs, but are also responsible in part for the drug's pharmacologic response (e.g., furosemide), drug‐drug interactions of therapeutic or toxic importance, and drug nephrotox

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03022.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A MEDLINE search of the National Library of Medicine data base from 1966–1994 was performed to review the anatomy and pathophysiology of intractable hiccups and their nondrug and drug therapies. Pertinent articles were further reviewed for older references and related literature. The infrequent occurrence of intractable hiccups makes it difficult to perform large, well‐controlled clinical trials. The only approved drug for the disorder, chlorpromazine, may not be acceptable for every patient. Studies have been conducted with metoclopramide, valproic acid, nifedipine, and baclofen as alternative therap

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03023.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Original research, reviews, and case reports discussing viral infectivity of blood‐ and plasma‐derived products were reviewed to determine the potential viral infectivity of human serum albumin (HSA) and plasma protein fraction (PPF). Data concerning viral infectivity, viral screening and inactivation procedures, and viral outbreaks associated with blood and plasma products were extracted and evaluated for pertinence to HSA and PPF. The starting material used for fractionation, the manufacturing process, postmanufacturing handling, and immunocompetence of HSA or PPF recipients were assessed to determine risk of symptomatic viral disease after transfusion. Both HSA and PPF are manufactured with pasteurization procedures that have led to an excellent viral safety record based on 50 years of clinical use. One outbreak of hepatitis B was associated with PPF as a result of an unreliable manufacturing process that has been corrected. The pasteurization process is effective in eradicating known viral pathogens when good manufacturing practices are followed. Continued surveillance of such products is warranted for viruses not included in routine screening procedures and for those that are resistant to current inactivation meth

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03024.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Pure red cell aplasia (PRCA) is an uncommon hematologic disorder characterized by the absence of erythroblasts in otherwise normal bone marrow. It is commonly an autoimmune disorder sometimes associated with a congenital error. It may also be acquired in association with thymomas, hematologic malignancies, human parvovirus B19 infection, drugs, and other disease states. Thirty drugs have been implicated as causative in PRCA, but most literature reports describe only one or two patients. Data evaluating possible mechanisms of drug‐induced PRCA are extremely limited, with conflicting results from different investigators. The criteria we used were at least five patients reported, reports from at least three separate investigators, and a minimum of one case of probable causality or better using a published assessment scale. With these criteria, phenytoin, azathioprine, and isoniazid had sufficient evidence of causality. All three are documented causes of PRCA and should be considered in any case of selective erythrocyte aplasi

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03025.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Warfarin resistance is a rare phenomenon, and most of the related literature obtained in a MEDLINE search from 1964–1995 consists of case reports. Warfarin resistance may develop as a result of noncompliance, exogenous consumption of vitamin K, and concurrent ingestion of other agents known to decrease warfarin's effects. There are three documented cases of hereditary resistance and one case of loose documentation of hereditary resistance with confirmation of similar resistant patterns in family members. Data on two of the three cases may support the postulation that hereditary resistance may be caused by the presence of an abnormal receptor or enzyme that has an increased affinity for vitamin K. To date, this receptor or enzyme has not been identified. To assess a subtherapeutic dose response to oral anticoagulation, the clinician must consider many possible causes of resistance, such as noncompliance, drug interactions, laboratory error, or pharmacokinetic changes. Once these have been ruled out, it is possible to consider that a tissue resistance to warfarin may be responsibl

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03026.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objective. To evaluate the effect of an intentional alteration in infusion pump flow continuity on the hemodynamic stability of infants receiving either dobutamine or dopamine.Design. Prospective, open‐label study.Setting. A university‐affiliated children's hospital.Patients. Ten hemodynamically stable infants (age 2 wks–10 mo) in intensive care receiving dobutamine (5) or dopamine (5). Three patients received both agents and were studied at independent times.Interventions. Dobutamine and dopamine were administered using the Flo‐Gard VP pump that delivers an intentional alteration of flow continuity (rate pulse). Heart rate and mean arterial pressure (MAP) were recorded every second. Analysis was based on the measurements obtained from the first 5 minutes on the study pump and the 2 minutes before and after the rate pulse.Measurements and Main Results. Although hemodynamic changes in pre‐ and post‐rate pulses were statistically significant (p<0.05) in some individuals, only one infant had a greater that 10% change in MAP 2 minutes after the rate pulse. Alterations in hemodynamics were not consistent among or within patients.Conclusion. In infants requiring dobutamine or dopamine, no clinically significant pharmacodynamic effects were associated with alteration in continuity of drug delivery caused by the single positive rate pulse. Therefore, we conclude there is no contraindication to the use of this infusion pump in hemodynamically stable infants receiving

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03027.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objective. To examine the extent, variability, and factors affecting vancomycin protein binding.Design. Prospective, open‐label, cohort study.Setting. A general hospital.Patients. Forty‐four adults [mean (± SD) age 50.9 ± 17.1 yrs, range 16.8–92.0 yrs] with serious infections.Interventions. Unbound (Vu) and total (Vtot) vancomycin concentrations were determined by fluorescence polarization immunoassay. A statistical analysis model used the maximum likelihood method to evaluate the association between several important variables and log Vuwhile controlling for log Vtoteffects.Measurements and Main Results. The mean fraction percentage of unbound vancomycin was 79.5 ± 6.0% (range 53.0–96.3%). While controlling for Vtotthe total variability of Vuwas 8.3%, suggesting that vancomycin binding is relatively constant in sick adults. We were able to demonstrate a significant statistical interaction effect between gender and globulin protein concentration on Vu(p = 0.022). Globulin protein concentration in men was negatively associated with Vu(p = 0.0009), but there was no association in women (p = 0.645). Age, race, peak‐trough association, serum creatinine, serum albumin, serum prealbumin, and hemodialysis were not significantly associated with log Vuin the statistical model.Conclusion. Compared with earlier studies in healthy adults, vancomycin binding appears to be decreased during acute illness, and intrapatient and interpatient variability are relatively small. Unbound vancomycin concentration appears to be gend

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03028.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objective. To compare the incidence ofPneumocystis cariniipneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV) receiving one of three prophylactic agents.Design. Retrospective chart review.Setting. A university‐affiliated Department of Veterans' Affairs medical center HIV clinic.Patients. All 200 HIV‐infected patients enrolled in the clinic who were prescribed a PCP prophylactic drug during 18 months.Interventions. Patients were administered oral trimethoprim‐sulfamethoxazole (TMP‐SMX) DS, oral dapsone, or aerosolized pentamidine in a heirarchic fashion. A subset of 110 patients received only one of the prophylaxis regimens for at least 6 months; they were examined separately for the purpose of statistical analysis.Measurements and Main Results. One case of PCP was diagnosed in 1110 patient‐months of oral TMP‐SMX DS therapy, 6 in 418 patient‐months of oral dapsone therapy, and 3 in 164 patient‐months of aerosolized pentamidine therapy. In the subset population, the documented incidence of PCP was 0% among 71 TMP‐SMX DS‐treated patients, 16% among 25 dapsone‐treated patients (p<0.004), and 14% among 14 aerosolized pentamidine‐treated patients (p<0.03). For patients receiving primary prophylaxis, the incidence of PCP was 0% for 58 receiving TMP‐SMX, 15% for 20 receiving dapsone (p = 0.015), and 17% for 6 receiving pentamidine (p = 0.094).Conclusion. We believe TMP‐SMX DS was more effective than oral dapsone or aerosolized pentamidine in preventing PCP in

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03029.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Study Objectives. We have shown in previous studies that epinephrine administered intranasally is a feasible route of administration during cardiopulmonary resuscitation (CPR). To promote the absorption of epinephrine we administered phentolamine prior to epinephrine and used a bile salt as a vehicle to dissolve the epinephrine. The purpose of this study was to compare the effect of two different vehicles (bile salt vs surfactant) in promoting the absorption of nasally administered epinephrine during CPR and to determine their effects on the nasal mucosa.Study Design. A randomized, blinded study.Setting. A controlled laboratory environment.Subjects. Eleven mongrel dogs.Interventions. Each dog underwent 3 minutes of unassisted ventricular fibrillation (VF) followed by 7 minutes of VF with CPR. Five minutes after the start of VF, 10 dogs received intranasal phentolamine 0.25 mg/kg/nostril followed 1 minute later by intranasal epinephrine 7.5 mg/kg/nostril. The epinephrine was dissolved in a randomly assigned vehicle consisting of either taurodeoxycholic acid (group A, bile salt) or polyoxyethylene‐9‐lauryl ether (group B, surfactant). One animal acted as a control and received 0.9% sodium chloride nasally.Measurements and Main Results. Data from eight dogs (one control) were included for analysis. Histology of the nasal cavity demonstrated severe multifocal erosion and ulceration of the respiratory epithelium for groups A and B compared with the control. The severity was similar between the two groups. In addition, no significant differences in plasma epinephrine concentrations or blood pressure responses were seen between the groups.Conclusion. Based on histology, polyoxyethylene‐9‐lauryl ether offered no advantage over taurodeoxycholic acid in its effect on the nasal mucosa. The data available for changes in epinephrine concentration and pressure also suggest no difference between the two vehicles in promoting the absorption of epinephrine during CPR in an anima

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03030.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The influence of grapefruit juice (GFJ) on caffeine's metabolism and the hemodynamic effects of this potential food interaction were studied in 10 normotensive volunteers. In this crossover study, caffeine (3.3 mg/kg) and water or caffeine and GFJ were given to participants. Nine serum caffeine concentrations were determined within 24 hours of each phase. In another phase of this study, caffeine was given with multiple GFJ doses to 6 of the 10 participants. Ambulatory blood pressure (BP) monitors were used for 12 hours to assess treatment hemodynamic effects. The mean area under the serum caffeine concentration‐time curve (AUC0–∞) values ± SD for the caffeine with water group, caffeine with GFJ group, and caffeine with multiple GFJ group were 47.0 ± 10.8, 48.7 ± 15.2, and 49.6 ± 7.0 μg/ml · hr, respectively (NS). There was no significant difference on the ambulatory systolic BP, diastolic BP, percentage of the time with a diastolic BP greater than 90 mm Hg, or heart rate area under the effect curves. We conclude that grapefruit juice had no effect on caffeine pharmacokinetics or hemodyna

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1996.tb03031.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY