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Efficacy of a long-acting formulation of ivermectin against Psoroptes ovis (Hering, 1838) on cattle.

A study was conducted in cattle experimentally infested with Psoroptes ovis to compare the prophylactic control against P. ovis provided by a long-acting injectable formulation of ivermectin to that of a commercially available injectable formulation of doramectin. Thirty Holstein steers were used. Animals were allocated by restricted randomization based on Day 0 body weight, forming six replicates of five animals each. Within each replicate, one animal was randomly allocated to one of the following treatment groups, with ivermectin and doramectin administered subcutaneously where indicated: (1) untreated controls; (2) ivermectin long-acting injectable (LAI) 630 mcg/kg, 56 days before challenge; (3) ivermectin LAI 630 mcg/kg, 42 days before challenge; (4) ivermectin LAI 630 mcg/kg, 35 days before challenge; or (5) doramectin 200 mcg/kg, 35 days before challenge. Animals were housed in individual pens 1 week prior to treatment. All animals were experimentally infested with P. ovis mites in the area between the shoulders, on the same day. Live mites were counted in scrapings from mange lesions at 2 sites on each animal 14, 21 and 28 days after challenge. Live mites were found in 33, 67 and 83% of the untreated controls on each respective evaluation. No P. ovis mites were found in steers treated with ivermectin LAI. Those animals showed lower (P < 0.05) mite counts than untreated controls on evaluations conducted 21 and 28 days after challenge. These results indicate that the ivermectin long-acting injectable formulation prevents induced infestations by P. ovis for at least 56 days after treatment. Doramectin injectable formulation, used at 200 mcg/kg, did not have a prophylactic effect 35 days after treatment.

Animals↗

Haemodynamics, cardiac conduction and pharmacokinetics of mibefradil (Ro 40-5967), a novel calcium antagonist.

OBJECTIVES: Mibefradil (Ro40-5967) is a chemically novel non-dihydropyridine calcium antagonist. In this phase II study we compared its acute and chronic effects on blood pressure, heart rate and atrioventricular conduction (electrocardiographic PQ interval) with those of verapamil and diltiazem. PATIENTS AND METHODS: After a 4-week placebo run-in, 18 patients with mild to moderate essential hypertension were given single doses of mibefradil (150 mg), slow-release (SR) verapamil (240 mg), diltiazem (240 mg) and placebo at weekly intervals; pharmacokinetics and the effects on blood pressure, heart rate and PQ interval were studied on four 10-h study days. Seventeen of the same patients subsequently underwent 4 weeks of treatment with either mibefradil (100 mg daily; n = 10) or verapamil SR (240 mg daily; n = 7), and on the last day, they attended a further 10-h study day. Two studies were conducted: an acute, single-dose, double-blind, randomly allocated, placebo-controlled, crossover study and a chronic, open-label, randomly allocated, parallel-group study. RESULTS: Mibefradil was well tolerated. In the acute study, the antihypertensive effect (difference from placebo) of mibefradil 150 mg was of slower onset than that of verapamil or diltiazem, but comparable blood pressure reductions had been achieved by 6 h. The mean +/- SD maximal PQ prolongation (difference from placebo) was 15.6 +/- 16.1 ms, compared with 44.0 +/- 22.6 ms for verapamil and 56.0 +/- 48.9 ms for diltiazem (P<0.05 mibefradil versus verapamil; P<0.01 mibefradil versus diltiazem). In the chronic study there were no significant differences during steady-state conditions between mibefradil at 100 mg and verapamil SR at 240 mg in their effects on blood pressure, PQ and heart rate. The mean +/- SD elimination half-life (t1/2) of mibefradil under steady-state conditions was 26.8 +/- 5.5 h (versus an apparent t1/2 of 16.9 +/- 11.1 h for verapamil SR, P<0.05). CONCLUSIONS: Mibefradil is a well-tolerated and efficacious antihypertensive agent well suited to single daily dosing because of its intrinsic long plasma half-life. The effects on both blood pressure and PQ interval are of more gradual onset than those of unmodified verapamil and diltiazem after single doses.

Adolescent↗

Guillotine and dissection tonsillectomy compared.

One hundred children and twenty adults were randomly allocated to guillotine or dissection tonsillectomy operations. The study was prospective and double-blind. In the children, the guillotine technique had demonstrable advantages over the dissection technique in terms of duration of operation, blood loss and post-operative pain. There was no significant morbidity in either group. In the adults, the random allocation of patients into these groups was found to be technically unsatisfactory and this arm of the study was abandoned after twenty patients.

Adolescent↗

Post-vaccination tuberculin sensitivity for assessing BCG vaccination in areas with high prevalence of non-specific sensitivity.

The relationship of non-specific sensitivity to post-vaccination tuberculin sensitivity has been the subject of controversy. This relationship has an important bearing on the common practice of using post-vaccination tuberculin sensitivity for assessing BCG vaccination in areas with a high prevalence of non-specific sensitivity. If post-vaccination tuberculin sensitivity is found to be dependent on the amount of already existing, naturally acquired, non-specific sensitivity it could not be considered a reliable measure of the success of BCG vaccination. In a recent BCG trial in India a large number of persons were tested with PPD-S and PPD-B and also vaccinated with BCG vaccine or injected with placebo, by random allocation. Mutually exclusive random samples of the study population were retested with PPD-S at 2 1/2 months, 2 1/2 years and 4 years after vaccination. At each post-vaccination test the tuberculin sensitivity obtained among the placebo-injected controls provided a measure of the tuberculin sensitivity due to non-specific sensitivity that would have been present in the absence of BCG vaccination. The difference between the mean size of reactions to the post-vaccination test among the vaccinated and among the unvaccinated controls provided a measure of tuberculin sensitivity that was wholly due to BCG vaccination. Thus it was possible to separate and study the two components of post-vaccination tuberculin sensitivity. The results of the study indicate that post-vaccination tuberculin sensitivity can be used to assess BCG vaccination in areas with a high prevalence of non-specific sensitivity, provided the assessment is done in younger age groups and based on post-vaccination tuberculin sensitivity as measured at 2-3 months after vaccination and not later.

Adolescent↗

Effects of microbial phytase supplementation on egg production, eggshell quality, and mineral retention of laying hens fed different levels of phosphorus.

A 20-wk feeding trial (21 to 40 wk of age) was conducted to evaluate the effects of phytase supplementation on egg production, egg quality, nutrient retention, and P excretion of laying hens fed diets containing different levels of P. Nine hundred and sixty ISA Brown hens were randomly allocated to completely randomized block arrangement of four diets: corn-soybean diet (1.4% tricalcium phosphate, TCP) without (T1, control) and with phytase (T2); 0.7% TCP (T3) or 0% TCP (T4) diet with phytase. Dietary microbial phytase was added at a level of 500 U/kg. Both hen-day and hen-housed egg production of T2 were significantly (P < 0.05) higher than other treatments, which were not different among themselves. Egg weights were also significantly (P < 0.05) different among treatments ,with T2 being the highest. Feed consumption of T2 was significantly (P < 0.05) higher than other treatments but feed conversion ratio was not significantly different from others. Specific gravity and shell thickness of the eggs were highest in the control (T1) but eggshell strength and broken egg to total egg ratio were not different among treatments. Haugh units were not different among treatments. Retention of Ca, P, Mg, Fe, and Zn were greater (P < 0.05) in phytase-supplemented groups. There were significant (P < 0.05) differences in excretion of ash, P, and Zn. The excretion of these components were highest in the control, whereas P excretion was significantly lower in the T3 and T4 groups. In conclusion, supplementation of the microbial phytase to normal corn-soybean diet improved egg production and can reduce TCP level in the diet without affecting egg production and egg quality. Significant reduction of P excretion can be also achieved.

6-Phytase↗

Effect of breast self-examination techniques on the risk of death from breast cancer.

OBJECTIVE: To measure the effect of breast self-examination (BSE) technique and frequency on the risk of death from breast cancer. DESIGN: Case-control study nested within the Canadian National Breast Screening Study (NBSS). SETTING: The Canadian NBSS, a multicentre randomized controlled trial of screening for breast cancer in Canadian women. SUBJECTS: The case subjects were 163 women who had died from breast cancer and 57 women with distant metastases. Ten control subjects matched by 5-year age group, screening centre, year of enrolment and random allocation group were randomly selected for each case subject. EXPOSURE MEASURES: Self-reported BSE frequency before enrolment in the NBSS, annual self-reports of BSE frequency during the program and annual objective assessments of BSE technique. OUTCOME MEASURES: Odds ratios (ORs) associated with BSE practice were estimated by conditional multiple logistic regression modelling, which permitted control of covariates. RESULTS: Relative to women who, when assessed 2 years before diagnosis, examined their breasts visually, used their finger pads for palpation and examined with their 3 middle fingers, the OR for death from breast cancer or distant metastatic disease for women who omitted 1, 2 or 3 of these components was 2.20 (95% confidence interval [CI] 1.30 to 3.71, p = 0.003). The OR for women who omitted 1 of the 3 components was 1.82 (95% CI 1.00 to 3.29, p = 0.05), for those who omitted 2 of the 3 components, 2.84 (95% CI 1.44 to 5.59, p = 0.003), and for those who omitted all 3 components, 2.95 (95% CI 1.19 to 7.30, p = 0.02). The results remained unchanged after adjustment for potential confounders. CONCLUSION: The results, obtained with the use of prospectively collected data, suggest that the performance of specific BSE components may reduce the risk of death from breast cancer.

Adult↗

Manchester regional breast study. Preliminary results.

1020 patients with early breast cancer were treated between March, 1970, and October, 1975, according to a prospective clinical trial. The results have been recorded after a follow-up of two to seven years. 713 cases of clinical stage-1 cancer were randomly allocated to treatment by simple mastectomy and postoperative radiotherapy, or simple mastectomy alone. There was no statistically significant difference in overall survival or in survival without distant metastases between the two groups. There was a significant reduction in the incidence of local recurrence in those who had received early postoperative radiotherapy compared with those who had not. 307 cases of clinical stage-11 cancer were randomly allocated to treatment by simple mastectomy and postoperative radiotherapy or radical mastectomy alone. There was no statistically significant difference in survival or in the incidence of local recurrence or distant metastases between the two groups.

Adult↗

[Adjuvant chemotherapy for gastric cancer--the third study. First report: central randomization by telephone method and analysis of patients' background factors].

JFMTC conducted the third adjuvant chemotherapy study for gastric cancer patients after curative surgery from 1982 to 1983. Patients were randomly allocated to one of the three arms by telephone method controlled at the headquarters of the foundation. This method resulted in the marked reduction of ineligible cases (253 cases, 6.0% of 4,236 cases), compared with those in the first study (18.3%). Main reasons of ineligibility were the violation of entry criteria due to the misjudgment of noncancer, duplicate cancers and operative curability. Telephone method for random allocation seems to contribute to the improvement in the data quality of a clinical trial.

Antineoplastic Combined Chemotherapy Protocols↗

Cefamandole and isoxazolyl penicillins in antibiotic prophylaxis of patients undergoing total hip or knee-joint arthroplasty.

In a prospective comparative clinical efficacy and safety study, 58 patients undergoing total hip or knee arthroplasty were randomly allocated to two groups; one received 29 cefamandole intravenously before operation and then 1 g every 6 h parenterally for 3 days and the other received 29 cloxacillin i.v. every 8 h for 1 day and 29 dicloxacillin perorally every 8 h for 2 days. Concentrations of cefamandole and cloxacillin were measured in the serum of all patients and in the synovial fluid of 28 patients. The serum C-reactive protein (CRP) level was measured in 16 randomly allocated patients preoperatively and daily for 8 days. In serum the concentrations of cefamandole and cloxacillin were high. The great variation in cloxacillin concentration can be due in part to its strong affinity for blood proteins. Cefamandole entered the synovial fluid of the knee joint at high concentrations in 5-15 min; similar concentrations of cloxacillin were measured after 16-30 min. Thus, cefamandole seems to be more recommendable as antibiotic prophylaxis in total hip and knee replacements. The CRP level decreased to below 60 mg/l in all 16 patients on the 6th postoperative day.

Aged↗

Changes in plasma potassium concentration during carbon dioxide pneumoperitoneum.

Hyperkalaemia with ECG changes had been noted during prolonged carbon dioxide pneumoperitoneum in pigs. We have compared plasma potassium concentrations during surgery in 11 patients allocated randomly to undergo either laparoscopic or open appendectomy and in another 17 patients allocated randomly to either carbon dioxide pneumoperitoneum or abdominal wall lifting for laparoscopic colectomy. Despite an increasing metabolic acidosis, prolonged carbon dioxide pneumoperitoneum resulted in only a slight increase in plasma potassium concentrations, which was both statistically and clinically insignificant. Thus hyperkalaemia is unlikely to develop in patients with normal renal function undergoing carbon dioxide pneumoperitoneum for laparoscopic surgery.

Adolescent↗

Effects of excess dietary leucine and leucine catabolites on growth and immune responses in weanling pigs.

Two experiments with weanling pigs were conducted to study the effects on growth and immune responses of excess dietary L-leucine (LEU) and dietary supplementation with the LEU catabolites, alpha-ketoisocaproic acid (KIC) and beta-hydroxymethyl butyrate (HMB). In Exp. 1, 80 pigs were randomly allocated according to initial BW and ancestry to five replications of four dietary treatments (four pigs/pen). The control diet contained wheat, oat groats, menhaden fish meal, and dried whey and provided 1.12% LEU. Treatment diets were the control plus 1.12% LEU, 1.12% KIC, or .4% HMB. The experiment lasted 6 wk. In Exp. 2, 36 pigs were randomly allocated to nine replications of four dietary treatments in a 2 x 2 factorial arrangement. Treatments consisted of two concentrations of dietary LEU and a daily i.m. injection of dexamethasone (DEX) or saline. Pigs were fed a control corn-soybean meal and dried whey diet (1.56% LEU) or the control diet plus 1.56% of crystalline LEU. Pigs were individually penned and the experiment lasted 4 wk. Growth performance, plasma free amino acids, plasma urea nitrogen, and humoral and cellular immune responses were measured. Results indicated that LEU concentrations in practical diets and supplementation with KIC and HMB (Exp. 1) did not detrimentally affect growth and immune response. The high LEU concentration and DEX injection used in Exp. 2, however, were detrimental to both growth and immune response.

3-Hydroxybutyric Acid↗

Field evaluation of a topical doramectin formulation for the chemoprophylaxis of parasitic bronchitis in calves.

A study was conducted to evaluate the efficacy of two topical treatments with doramectin on the season-long control of lungworm and gastrointestinal infections in first grazing season (FGS) calves. At the start of the study, 20 FGS calves were randomly allocated into two treatment groups of 10 animals each. Calves in the D-group were treated with doramectin pour-on on days 0 and 56, at a dosage of 500 microg kg(-1) BW: calves in the C-group were designated as controls. A permanent pasture was divided in two blocks and these were randomly allocated to the treatment groups. Throughout the study, tracers (n = 32) were grazed on each paddock at 3-week intervals. Clinical signs of parasitic bronchitis (PB) were observed in the C-group in July and this necessitated two salvage treatments with levamisole. From day 28, post-turnout lungworm larvae were recovered from faeces of the C-calves until housing. No signs of PB were observed in the D-group during the entire grazing season. Shedding of lungworm larvae in the principals of the D-group did not occur until 112 days post-turnout. From the data obtained from the tracer calves. it appeared that larvae had overwintered on both pastures. On the C-pasture, the number of lungworms recovered from the tracer calves gradually increased to a peak in September, whereas on the D-pasture, the increase was observed only at the end of the pasture season. Both strongyle faecal egg counts and pepsinogen levels were relatively low in both groups throughout the present study. At the end of the grazing period (day 161). the principals were housed and treated with oxfendazole. During the housing period, all principal animals (D- and C-groups) and a third group of four helminth free animals (N-group) received a challenge infection with Dictyocaulus viviparus. It appeared that the different exposure to the parasite during the grazing season resulted in different establishment rates, i.e.. group C < group D < group N. The present results show that overwintering of lungworm larvae occurs in Belgium and that in such conditions, doramectin pour-on given at turnout and at 8 weeks controls PB in calves during the first grazing season.

Administration, Topical↗

[A 13-week subchronic toxicity study of D-xylose in F344 rats].

A 13-week subchronic toxicity study of D-xylose was performed in male and female F344 rats at dose levels of 0%, 0.2%, 0.6%, 1.7%, and 5% D-xylose in the CRF-1 powder diet to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. No treated groups showed changes in body weight gain or food intake, and all animals survived until the end of the experiment. Hematological examination revealed significant increases in RBC, Hb, and Ht in the male groups treated with 0.6% and 5% concentrations, whereas these values decreased significantly in all of the female groups treated with D-xylose. However, no clear dose-response effect was observed in the hematological data in either males or females given D-xylose. Serum biochemistry studies revealed decreases in AsT in the 0.2% and 5% D-xylose group male and 0.2%, 1.7%, and 5% group female, compared to the control value. However, the changes were not considered specific because of the lack of any clear dose-response effect. In addition, no histopathological changes indicating obvious toxicity of D-xylose were observed in the livers of either sex treated with D-xylose. Based on these data, the MTD of D-xylose in F344 rats of both sexes is judged to be 5% or more in the diet.

Administration, Oral↗

Anthelmintic resistance on goat farms in Georgia: efficacy of anthelmintics against gastrointestinal nematodes in two selected goat herds.

Gastrointestinal nematode (GIN) parasitism is a major constraint to production of goats in the southeastern United States. The conventional method of control used by producers in this region is frequent use of anthelmintics during the warm season. Overuse of anthelmintics has led to an increase in the incidence of anthelmintic resistance in many parts of the world, but data on prevalence of anthelmintic resistance in GIN of goats in the southeastern United States are very limited. To address this issue, anthelmintic efficacy was determined in goat herds at the Fort Valley State University, Agricultural Research Station (FVSU-ARS) and the University of Georgia, College of Veterinary Medicine (UGA-CVM) using fecal egg count reduction (FECR) tests and DrenchRite((R)) larval development assays (LDA). At FVSU-ARS, 2-year-old Spanish goat does were randomly allocated to one of nine different treatment groups (n = 10): albendazole (ABZ; 20mg/kg body weight (BW)), fenbendazole (FBZ; 20mg/kg BW), ivermectin (IVM; 0.4 mg/kg BW), doramectin (DRM; 0.4 mg/kg BW), moxidectin (MOX; 0.4 mg/kg BW), levamisole (LEV; 12 mg/kg BW), morantel tartrate (MOR; 10mg/kg BW), a combination of IVM (0.4 mg/kg BW) and ABZ (20 mg/kg BW), and untreated controls. At UGA-CVM, goats were randomly allocated to one of five different treatment groups (n = 8): ABZ (20 mg/kg BW), IVM (0.4 mg/kg BW), MOX (0.4 mg/kg BW), LEV (12 mg/kg BW), and untreated controls. All drugs in both experiments were administered orally. Anthelmintic efficacy was calculated by comparing 14-day post-treatment FEC of treated and control animals, and percent reductions were interpreted using the World Association for the Advancement of Veterinary Parasitology guidelines for resistance. For the LDA, nematode eggs were isolated from pooled fecal samples of untreated control goats in each herd and used to perform DrenchRite((R)) assays. In the FVSU-ARS herd, MOX, LEV, the combination of IVM and ABZ, IVM, DRM, ABZ, MOR, and FBZ reduced FEC by 100, 91, 88, 78, 76, 62, 48, and 10%, respectively. In the UGA-CVM herd, MOX, LEV, ABZ and IVM, reduced FEC by 100, 94, 87, and 0%, respectively. In both herds moxidectin was the only drug tested that was fully effective. Results of the LDA were in agreement with results of the FECR tests for both herds. These data demonstrate the presence of GINs resistant to all three major anthelmintic classes in both goat herds.

Animals↗

Efficacy of clavulanate-potentiated amoxycillin in experimental and clinical skin infections.

The efficacy of clavulanate-potentiated amoxycillin was compared with amoxycillin alone in experimental staphylococcal infection in dogs and in a controlled trial in clinical cases of skin infection in dogs and cats. The experimental infection was produced by subdermal inoculation with beta-lactamase producing (amoxycillin resistant) staphylococci absorbed in cotton dust. This produced discrete, localised lesions with no systemic involvement. In a cross over study, six animals were randomly allocated to treatment with either amoxycillin alone (10 mg/kg, dosed twice daily) or a formulation of clavulanate-potentiated amoxycillin (12.5 mg/kg, of a 1:4 ratio, dosed twice daily). The lesions of the animals treated with clavulanate-potentiated amoxycillin resolved more quickly than those treated with amoxycillin alone. The difference was significant (P less than 0.05) for both lesion diameter and inflammation score after day 6 of treatment. A trial was carried out in clinical cases of skin disease which were randomly allocated to twice daily treatment with either amoxycillin alone (10 or 20 mg/kg), or with clavulanate-potentiated amoxycillin (12.5 or 25 mg/kg of a 1:4 ratio). The required duration of treatment was shorter (P less than 0.5) for the potentiated amoxycillin treatments, and the success rate (judged by cure or substantial improvement) was higher (P less than 0.05) for this group, especially (P less than 0.01) where amoxycillin resistant organisms were isolated. It was concluded that clavulanate-potentiated amoxycillin was an effective treatment of skin infections both under experimental and clinical conditions.

Amoxicillin↗

Temporal relationship between the onset of oestrus, the preovulatory LH surge and ovulation in farmed fallow deer, Dama dama.

A study was conducted to determine the timing of ovulation relative to the onset of oestrus and the preovulatory LH surge in fallow deer. Mature fallow does were randomly allocated to two treatments (N = 10 per treatment) designed to synchronize oestrus on or about 17 May. Does assigned to Group 1 (prostaglandin-induced oestrus) each initially received single intravaginal CIDR [Controlled Internal Drug Release] devices for 13 days followed by an i.m. injection of 750 mg cloprostenol on Day 12 (15 May) of the subsequent luteal cycle. Does assigned to Group 2 (progesterone-induced oestrus) each received CIDR devices for 13 days, with withdrawal occurring on 15 May. All does were run with crayon-harnessed bucks (10:1 ratio) from the start of synchronization (18:00 h 15 May). Ten does (5 per group) were blood sampled via indwelling jugular cannulae every 2 h for 72 h from cloprostenol injection or CIDR device withdrawal and the plasma was analysed for concentrations of progesterone and LH by radioimmunoassay. Does within each treatment were randomly allocated to an ovarian examination time of 12, 16, 20 or 24 h after the onset of oestrus. Laparoscopy was repeated at 12-h intervals until ovulation was recorded. The ovaries of does failing to exhibit oestrus were examined 72 and 86 h after cloprostenol injection or CIDR device withdrawal. A total of 17 does were observed to exhibit oestrus at a mean (+/- s.e.m.) interval from treatment of 44.6 +/- 3.6 h for Group 1 (N = 9) and 34.1 +/- 2.5 h for Group 2 (N = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Strategies for mastitis control: dry cow therapy and culling.

The effects of three selection strategies for dry cow therapy on prevention of new infections and rate of antibiotic usage were compared. Quarter infection status of 1044 cows in 12 herds was determined by bacteriological methods at drying off, calving and three to five months into the following lactation. Cows that were uninfected at drying off were randomly allocated to treatment (whole udder, dry cow therapy) and non-treatment groups. Infected cows were randomly allocated to whole udder or infected quarter only treatments. The strategies compared were blanket treatment (treat all quarters of all cows), selective cow treatment (treat all quarters of any cow infected in one or more quarters) and selective quarter treatment (treat infected quarters only). Selective cow treatment was identified as the preferred strategy. Blanket treatment resulted in increased antibiotic usage (15.5 vs 6.4 tubes per infection eliminated) with no additional benefit, and selective quarter treatment resulted in a higher new infection rate (6.4% vs 3.9% quarters) in the dry period. The prevalence of infection within a herd at drying off had no influence on new infection rates in the dry period or early lactation. The cure rate after dry cow treatment (mean of 66%) decreased significantly with increasing age (P < 0.001). Cows infected in the previous lactation contributed over 76% of infections at calving and nearly 70% at mid-lactation. To lower the incidence of mastitis in a herd, a greater emphasis on culling of older infected cows and prevention of new infections during lactation is needed.

Animals↗

Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.

OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. STUDY DESIGN: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. RESULTS: Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.

Adult↗