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1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated. [ABSTRACT FROM AUTHOR]

Enalapril is the result of a targeted research programme to develop a non-mercapto converting enzyme inhibitor with a long duration of action and an improved safety profile for use in the therapy of hypertension and congestive heart failure. Over 3500 patients world-wide have received enalapril or enalaprilat. Long-term experience at present includes over 2500 patients. While enalapril and captopril produce similar efficacy, enalapril is better tolerated and appears not to be associated with occurrence of captopril-type side-effects, particularly the skin rash, taste loss, leukopenia and proteinuria. Enalapril and other converting enzyme inhibitors may be associated with renal insufficiency when given to patients with bilateral renovascular hypertension. [ABSTRACT FROM AUTHOR]

Hypoalbuminemia and decreased colloid osmotic pressure (COP) are common in critically ill dogs. Hypoalbuminemia has been shown to negatively impact outcome. Treatment strategies to raise COP include the use of both natural and synthetic colloids. To date there is no comprehensive evaluation of human albumin (HA) use in dogs. The purpose of this retrospective study was to evaluate the use of 25% HA in critically ill dogs. The medical records of all dogs receiving HA between January 2003 and March 2004 were reviewed using a standardized data sheet for signalment, diagnoses, Survival Prediction Index (SPI), dose of HA administered, amount of crystalloid fluid administered prior to HA administration, length of hospitalization (LOH), complications, and outcome. Additionally pre- and post-HA administration values for serum albumin (SA), blood COP, and total solids (TS) were evaluated. Thirty-seven dogs received HA. Thirty of the 37 dogs (81%) underwent surgery and 13 of 37 (39%) dogs were diagnosed with septic peritonitis. Other diagnoses included trauma, wounds, neoplasia, gastric ulcer, and pancreatitis. The median SPI of all dogs was 0.53 (range 0.06–0.82). Median dose of HA used was 1.5 g/kg (range 0.38–3.64 g/kg). Median dose of crystalloid fluids administered prior to HA administration was 6.23 ml/kg/hr (range 1.2–45.4 ml/kg/hr). Median LOH was 5 days (range 1–16 days). Mild complications were encountered in 9 of 37 (24%) dogs and included prolonged clotting times (n=3), increased breathing effort (n=3), vomiting (n=2), and fever (n=1). Of the 37 dogs in the study, 21 (57%) survived, 10 (27%) died, and 6 (16%) were euthanized. After HA administration, median SA increased from 1.5 g/dl (range 1.0–2.1 g/dl) to 2.8 g/dl (range 1.5–4.4 g/dl) (p<0.001), median COP increased from 11 mmHg (range 6.8–13.8 mmHg) to 14.4 mmHg (range 11–26.9 mmHg) (p<0.001), and median TS increased from 2.9 g/dl (range 0.9–4.6 g/dl) to 4.0 (range 2.8–6.2) (p<0.001). When compared to non-survivors, survivors had higher post-HA administration SA (p=0.008), higher net COP increase (p=0.032), and received higher dosages of HA (p=0.046). Pre-treatment SA, COP, or the development of complications during administration did not impact LOH or outcome. In this retrospective study, HA administration effectively increased SA, TS and COP in critically ill dogs and was associated with relatively few complications. Future studies are warranted to further evaluate the potential benefits of HA administration. [ABSTRACT FROM AUTHOR]

Study Objective: Because the incidence rate of renal impairment is 2-10% for patients treated with high-dose methotrexate and renal impairment develops in 0-12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination., Design: Pooled analysis of efficacy data from four multicenter single-arm compassionate-use clinical trials using protocols from 1993 to 2007., Patients: Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 μmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement., Measurements and Main Results: Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1 μmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20 years (range 5 weeks-84 years). Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 μmol/L. At the first (median 15 minutes) through the last (median 40 hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase administration., Conclusion: Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients., (© 2013 Pharmacotherapy Publications, Inc.)