ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03959.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Life‐threatening thrombo‐occlusive events producing heart attacks and strokes develop in patients at sites of atherosclerotic arterial stenoses when plaques rupture, a process resistant to both aspirin and heparin. Resistant thrombotic complications are also troublesome during therapeutic thrombolytic or mechanical interventions for symptomatic atherosclerotic vascular disease, including angioplasty, various types of atherectomies, endarterectomy, endovascular stent deployment, or implanted small caliber vascular grafts. In this review therapeutic strategies for more effective management of these resistant, platelet‐dependent, occlusive thrombi are discussed, including: a) inhibition of platelet recruitment by anti‐GPIIb/IIIa monoclonal antibodies, naturally occurring peptides containing RGD sequences, or synthetic competitive analogs; b) direct inactivation of thrombin bound to thrombus by natural or synthetic antithrombin peptides; c) interruption of thrombin's production by natural or synthetic antagonists of Factor Xa or extrinsic and intrinsic coagulation pathways; and d) elimination of thrombogenicity at sites of vascular injury by immediately restoring confluent endothelium or prior therapy with dietary n‐3 fatty acids. However, antagonists of both GPIIb/IIIa‐ and thrombin‐dependent platelet recruitment produce equivalent inhibition of thrombus formation and platelet hemostatic function. Interestingly, hemostasis is spared by therapies that inhibit thrombin's production. Recommendations for development strategies are related to the relative hemostatic risks and antithromb

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03960.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Providing care to human immunodeficiency virus (HIV)‐infected children requires a comprehensive, multidisciplinary approach. This review will address the current status of supportive care, treatment of HIV‐associated complications and specific antiretroviral therapy. HIV affects multiple locations in the body resulting in a myriad of possible complications. These include opportunistic infections and malignancies secondary to immunodeficiency and central nervous system or other specific organ‐related disease secondary to direct HIV involvement. Recent scientific advances have markedly enhanced the quantity and quality of life of HIV‐infected children. Prophylaxis of Pneumocystis carinii pneumonia is the single most important therapeutic advance for the HIV‐infected patient. Other advances for the treatment and prevention of HIV‐related infections should similarly improve survival and reduce hospital stays. Antiretroviral therapy is relatively new. The currently available nucleoside reverse transcriptase inhibitors have proven efficacy. The role of single agents or combinations is being established. However, this group of antivirals has limitations that make alternate approaches essential. Augmentation of the patient's immune response will likely be a key to any future successful treatm

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03961.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Twenty‐three children, aged 8 to 14 years, with postoperative pain, were randomly assigned to receive a fixed 250‐mg dose (4.66–7.58 mg/kg) of naproxen as either a liquid suspension or tablet. After an overnight fast, the serum concentrations were measured before and at 0.5,1,2,3,4, 8,12,18, and 24 hours after administration of naproxen. The concentration versus time data were best fit to a one‐compartment open model. The area under the concentration versus time curve, apparent volume of distribution (VDss/F), and elimination parameters (CL/F, Ke, elimination half‐life) were similar in children who received suspension or tablets. Although the apparent maximum peak plasma concentration (Cmax) was greater in children who received tablets compared with those who received the suspension, Cmax/area under the curve (AUC), apparent time to maximum peak concentration (tmax), Ka, and estimated time to 10%, 50%, and 90% absorption (T10, T50, T90) were not different. The dose range was relatively narrow; hence, direct relationships between dose and elimination parameters, VDss/F, apparent tmax, Ka, T10, T50 or T90 were not observed. Neither VDss/F or CL/F were age related over the relatively narrow range of ages that were studied. Elimination of naproxen in our patients was more rapid than has previously been reported in children or adults, however. From a practical standpoint, naproxen tablets and suspension seem to be bioequivalent in fasting children ages 8 to

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03962.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Colloids are useful in cardiac surgery to increase preload and improve cardiac output without the risks associated with blood transfusions. Pentastarch is a new low‐molecular weight hydroxyethyl starch compound under investigation for this purpose. The authors compared, in a randomized fashion, 12 patients who received pentastarch and 17 patients who received albumin for volume expansion after open‐heart surgery. During the 24‐hour study period there was no significant difference between the two groups with respect to systemic blood pressure, mean arterial pressure, cardiac index, right atrial pressure, and pulmonary capillary wedge pressure, with the exception of a higher mean arterial pressure and systolic blood pressure at 4 hours in the albumin group and higher heart rate at 12 hours in the pentastarch group. In addition, postoperative prothrombin time, partial thromboplastin time, fibrinogen, platelets, and factor VIII levels were not significantly different between the two groups. There were no complications attributed to colloid administration. The hemodynamic parameters were further evaluated in a subset of 6 pentastarch and 9 albumin patients who received the first 500 mL of colloid in a similar time frame and under similar clinical conditions. The patients who received pentastarch showed a significantly greater increase in cardiac index than did the patients who received albumin. No significant change in other parameters were noted between the two groups. The authors conclude that pentastarch is as safe as albumin and may be a more effective volume expander than albumin when used in open‐heart surgery p

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03963.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A selective thromboxane (TX) synthase inhibitor, CS‐518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma induced by arachidonic acid (AA) and adenosine diphosphate (ADP) ex vivo were examined. The production of TXB2and 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) in serum during whole Wood coagulation ex vivo also were examined. In the single‐dose study (50, 100, and 200 mg), plasma concentrations of the drug were well fitted to a one‐compartment open model with first‐order absorption. The area under plasma concentration curve (AUC) and maximum plasma concentration (Cmax) showed dose‐related increases, whereas the mean elimination half‐lives remained rather constant (.68‐.92 hour). The drug was recovered in urine by 32 to 37% and 62 to 65% as unchanged and conjugated forms (acylglucuronide), respectively, showing almost complete absorption of CS‐518. The effect of food intake on the pharmacokinetics of CS‐518 was determined at the dose of 100 mg. The time to reach Cmax was prolonged from .42 to 2.08 hours and the Cmax was decreased by about 66%, whereas the AUC and urinary recovery showed no significant changes. The platelet aggregation in plasma induced by AA was markedly inhibited, whereas the secondary aggregation induced by ADP was inhibited to a much less degree. Platelet aggregation by AA was almost completely inhibited 2 hours after administration of any dose and the duration for maintaining the significant inhibition tended to depend on the dose ranging from 48 to 72 hours after administration, which was much longer than expected from the plasma concentration of drug. The inhibition of TX synthase was more markedly shown in the decreased production of TXB2and reciprocally increased production of 6‐keto‐PGF1α in serum during whole blood coagulation, which peaked at 1 hour and lasted until 3 to 7 days after administration, depending on the dose. In the multiple‐dose study (100 mg, twice daily, for 4.5 days), drug concentrations in plasma after each administration showed a good conformity with the simulation curve worked out using the pharmacokinetic parameters obtained after the initial dose, indicating that repeated administrations did not result in accumulation. Throughout the administration period, almost complete inhibition of platelet aggregation by AA was maintained and continued until 48 hours after the last administration, and a significant inhibition lasted more than 72 hours, which appeared much longer than expected from the plasma concentration of CS‐518. No abnormality attributable to the test drug was found in the routine laboratory tests, subjective and objective findings, vital signs including blood pressure, pulse rate and body temperature, and electrocardiogram. Oral administration of CS‐518 was concluded to be well tolerated with long‐lasti

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03964.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The authors examined the efficacy and safety of the combination of verapamil and nifedipine in the control of hypertension. Retrospective analysis of blood pressures was obtained on 50 patients who had historically documented essential hypertension and were receiving verapamil and nifedipine. The patients had moderate to severe hypertension; 27 of 50 (54%) were uncontrolled on prescribed regimens of two or more separate classes of drugs. Control was defined by the ability to maintain a blood pressure of ≤ 160/90 by providing doses of verapamil (max: 480 mg/day) and nifedipine (max: 180 mg/day). Twenty‐nine (50%) were black and 21 (42%) were white. Ages ranged from 16 to 84 years. Mean duration of therapy was 1–2 years. Only 3 of 50 (6%) were control failures after providing verapamil and nifedipine. Three of 50 (6%) were discontinued because of side effects — reversible hepatitis (2) and rash (1). There were no serious adverse events, i.e., CHF or arrhythmias. Manageable ankle edema was seen in 14 of 50 (28%) patients. Verapamil and nifedipine, a combination of a dihydropyridine and a non‐dihydropyridine calcium antagonist, was effective and safe in this group of patients with difficult‐to‐manage

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03965.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of N4‐behenoyl‐1‐β‐D‐arabinofuranosylcytosine (BHAC), a lipophilic antitumor analog of 1‐β‐D‐arabinofuranosylcytosine (ara‐C), was investigated, by assay of plasma and leukemic cells of ten acute leukemic patients receiving 60‐minute intravenous (IV) infusion of 700 mg/m2BHAC, for BHAC and 1‐β‐D‐arabinofuranosylcytosine 5′‐triphosphate (ara‐CTP) by high‐performance liquid chromatography, ara‐C by radioimmunoassay, and 1‐β‐D‐arabinofuranosyluracil (ara‐U) by gas chromatography‐mass fragmentography. The plasma concentration of BHAC reached a maximum (173.4 ± 75.3 μg/mL) at the end of the infusion and then declined in a biphasic pattern with an initial‐phase half‐life (t1/2α) of 1.00 ± .36 hours and a second‐phase half‐life (t1/2β) of 4.28 ± 2.35 hours. That of ara‐C similarly reached a maximum (102.2 ± 39.9 mg/mL) at the end of the infusion and then declined with t1/2α of 1.37 ± 1.11 hours and t1/2β of 11.2 ± 4.31 hours. Intracellular ara‐CTP concentration increased in a linear‐accumulation manner for the first 4 hours after the infusion, reached a maximum of .081 ± .112 μg/107cells at approximately 7 hours, and then declined very slowl

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03966.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The pharmacokinetics of cyclosporine (CSA) and four metabolites were evaluated in eight hemodialysis subjects awaiting renal transplantation to compare metabolic patterns with those observed in post‐transplant patients and normal volunteers. Each subject received a single 4‐mg/kg intravenous and a single 10‐mg/kg oral dose separated by a 1‐week washout period. Blood samples were collected before and at .5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, and 24 hours after CSA dosing. Cyclosporine blood, plasma, and metabolite (M17, M1, M18, M21) levels were determined by high‐pressure liquid chromatography. Mean (±standard deviation) CSA blood clearance was .47 ± .15 L/hour/kg, steady‐state volume of distribution (Vss) was 1.9 ± .5 L/kg, and mean residence time (MRT) was 4.4 ± 1.8 hours after intravenous dosing. With plasma, mean clearance was .70 ± .31 L/hour/kg, Vsswas 2.4 ±1.2 L/kg, and MRT was 3.7 ± 2.2 hours. Cyclosporine bioavailability (F) averaged 24 ± 11 and 24 ± 15%, using blood and plasma, respectively. Values for clearance and Vsswere approximately 30 to 100% greater than comparable estimates in healthy volunteers, but F and MRT were not altered to this extent. These changes might be explained on the basis of decreased protein binding in uremic patients. The area under the curve ratio for M17 and M1 to CSA increased an average of 1.7‐ and 3.9‐fold, respectively, after oral dosing compared with intravenous administration, indicating increased conversion duri

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03967.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03968.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY