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Benazepril and weight - long- was:Benzapril versus Enalapril

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  • nala nala
    Hi, Both enalapril and benazepril are ACE-inhibitors, but they are not the same drug. I am not familiar with any feline study directly comparing one to the
    Message 1 of 1 , Oct 4, 2007
      Hi,

      Both enalapril and benazepril are ACE-inhibitors, but
      they are
      not the same drug. I am not familiar with any feline
      study
      directly comparing one to the other, but I have not
      been keeping
      as careful a watch on feline veterinary literature as
      I once was.

      As far as benazepril and increased appetite I have
      excerpted sections
      of the study that you most likely refered to. (I have
      a copy
      of the study if anyone would like one).

      J Vet Pharmacol Ther. 2006 Jun;29(3):225-7
      Benazepril increases feed intake and body weight in
      healthy growing cats
      J. N. KING*,
      W. SEEWALD*,
      S. KING &
      E. GOLDENTHAL
      *Novartis Animal Health Inc., Basel, Switzerland;
      Novartis Animal Health Inc., Greensboro, NC, USA; MPI
      Research, Mattawan, MI, USA

      Twenty-four ... cats aged approximately 7 months and
      weighing 2.5–4.5 kg ... were randomized into groups.
      Six female and six male cats were dosed with 2 mg/ kg
      benazepril.HCl (FORTEKOR 5, Novartis Animal Health
      Inc., Basel, Switzerland) orally once daily for 52
      weeks. The dosage represents a small overdose when
      compared with the therapeutic dosage of 0.5–1 mg/kg of
      benazepril.HCl in cats (The BENRIC Study Group, 2006).
      The control group consisted of six female
      and six male cats, which were sham-dosed each day (the
      identical procedures were followed as for oral dosing
      with
      benazepril but no test article was administered).

      Cats ... were fed a complete commercial diet
      (Certified Cat Chow #5003, PMI Nutrition
      International Inc.,
      St Louis, Mo, USA). Water was provided ad libitum.

      Statistical analyses were conducted using repeated
      measures
      ANOVA. Significance was defined with P < 0.05.

      Body weights (P ¼ 0.39) and food consumption (P ¼
      0.64)
      were not significantly different between the
      benazepril and
      control groups at baseline, but were significantly
      higher in the
      benazepril group during treatment (Figs 1 and 2) with
      P ¼ 0.03
      for body weight and P < 0.0001 for food consumption.
      group.

      Although there were marked differences in body weights
      between males and female cats, significantly (P <
      0.05) higher
      body weights were observed in the benazepril group for
      both
      males and females.

      Food consumption was significantly
      higher in benazepril-treated animals when compared
      with the
      control group in male cats (+13.9%, P < 0.0001), but
      significance was not reached in female (+11.6%, P >
      0.05) cats.

      Secondly, ACEI have been reported to increase appetite
      or
      inhibit loss of body weight in patients with chronic
      heart failure.
      Benazepril increased appetite in dogs with congestive
      heart
      failure in one clinical trial (Kitagawa et al., 1997).
      In humans
      with chronic heart disease, ACEI reduce the risk of
      weight loss
      and possible mechanisms include reduction of levels of
      catecholamines
      or the inflammatory mediators tumour necrosis factor
      (TNF) or C-reactive protein (Anker et al., 2003).
      However, an
      alternative mechanism for improved appetite in
      patients with
      congestive heart failure could be secondary to
      increased
      cardiovascular function. However, we judge it unlikely
      that
      increased cardiovascular function or reduced
      inflammatory
      mediators played a significant role in increasing the
      food intake
      and body weight of the cats in our study as they were
      healthy
      animals.

      Increased food intake or body weights have not been
      reported
      previously with other ACEI in cats, dogs or rodents.
      In fact high
      doses of some ACEI may reduce appetite or body weight
      (Shimizu
      et al., 1993; Donaubauer & Mayer, 1988). No effects of
      treatment with enalapril (body weight) or imadapril
      (body
      weight or food consumption) were observed in healthy
      cats
      (Sanders et al., 1992; Thoulon et al., 2003).
      Therefore, it seems
      possible that the effects noted in our trial with
      benazepril are due
      to an additional property of this molecule in cats and
      do not
      reflect a class effect of ACEI in this species.

      Cats with heart or kidney disease frequently have
      reduced
      appetite and/or poor body condition and therefore
      benazepril
      would be useful clinically if it increased food
      consumption and/or
      body weight in diseased animals. It must be
      emphasized,
      however, that the cats in our study were young
      (approximately
      7 months), growing and healthy, and the same effects
      might not
      occur in older, diseased or convalescent cats.
      However, benazepril
      increased appetite in highly proteinuric (urine
      protein-tocreatinine
      ratio [UPC]P1) cats with chronic kidney disease,
      although no significant effects on either appetite or
      body weight
      were observed in animals with UPC < 1 (The BENRIC
      Study
      Group, 2006).


      There are also a couple of recent studies regarding
      benazepril
      and renal failure. Again, there was no comparison to
      other
      ACE-inhibitors. I do not have copies of these
      articles.
      -----
      J Vet Intern Med. 2006 Sep-Oct;20(5):1074-9.
      Evaluation of the clinical efficacy of benazepril in
      the treatment of chronic renal insufficiency in cats.

      Mizutani H, Koyama H, Watanabe T, Kitagawa H, Nakano
      M, Kajiwara K, King JN.
      Division of Veterinary Internal Medicine, Nippon
      Veterinary and Life Science University, Tokyo, Japan.

      BACKGROUND: Chronic renal insufficiency (CRI) is a
      common disease in cats. Angiotensin-converting enzyme
      inhibitors (ACEI) have beneficial effects in humans
      with CRI by reducing the loss of protein in the urine
      and increasing life expectancy. HYPOTHESIS: The ACEI
      benazepril has beneficial effects on survival,
      clinical variables, or both as compared with placebo
      in cats with CRI. ANIMALS: 61 cats with naturally
      occurring CRI.
      METHODS: The cats were enrolled into a prospective,
      randomized, double-blind, placebo-controlled clinical
      trial. Cats received placebo or 0.5-1 mg/kg benazepril
      once daily for up to 6 months.
      RESULTS: Urine protein/urine creatinine ratios were
      significantly (P < .05) lower with benazepril as
      compared with placebo at days 120 and 180. Three cats
      with placebo and 1 cat with benazepril were removed
      prematurely from the study because of deterioration of
      CRI or death. Cats were classified into 4 stages of
      CRI according to the International Renal Interest
      Society (IRIS) classification scheme. Incidence rates
      of cats with IRIS classification stage 2 or stage 3
      that remained in stage 2 or 3 without progressing to
      stage 4 were higher with benazepril (93 +/- 5%) as
      compared with placebo (73 +/- 13%).
      CLINICAL IMPORTANCE: These results suggest a potential
      for benazepril to delay the progression of disease,
      extend survival time, or both in cats with CRI.
      ---
      This study is from Novartis again - the maker of the
      drug.
      I have read that an artificial kidney failure system
      is used by
      this group that may or may not reflect natural
      disease.

      J Vet Intern Med. 2006 Sep-Oct;20(5):1054-64.

      Tolerability and efficacy of benazepril in cats with
      chronic kidney disease.

      King JN, Gunn-Moore DA, Tasker S, Gleadhill A,
      Strehlau G; Benazepril in Renal Insufficiency in Cats
      Study Group.
      Novartis Animal Health Inc, Postfach, Basel,
      Switzerland.

      The objective of the study was to test the effect of
      the angiotensin-converting enzyme inhibitor (ACEI)
      benazepril in cats with chronic kidney disease (CKD).
      A total of 192 cats with CKD with an initial plasma
      creatinine concentration > or = 2 mg/dL (> or = 177
      micromol/L) and urine specific gravity < or = 1.025
      were recruited into a double-blind, parallel-group,
      prospective, randomized clinical trial. Cats received
      daily (q24h) PO placebo (n = 96) or benazepril x HCl
      at a dosage of 0.5-1.0 mg/kg (n = 96) for up to 1,119
      days. Most cats were fed exclusively a diet containing
      low amounts of phosphate, protein, and sodium.
      Benazepril produced a significant reduction in
      proteinuria, assessed by the urine
      protein-to-creatinine ratio (UPC, P = .005). This
      effect of benazepril was present in all subgroups
      tested, including cats with UPC <0.2, although the
      effect was largest in cats with higher UPCs. Plasma
      protein was maintained at higher concentrations with
      benazepril as compared with placebo during treatment
      in cats with initial UPC <1 (P = .038 versus P = .079
      for all cats). There was no difference in renal
      survival time between the 2 groups when all 192 cats
      were compared. Mean +/- SD renal survival times were
      637 +/- 480 days with benazepril and 520 +/- 323 days
      with placebo (P = .47). Mean +/- SD renal survival
      times in the 13 cats with initial UPC > or = 1 were
      402 +/- 202 days with benazepril and 149 +/- 90 days
      with placebo (P = .27). Cats with initial UPC > or = 1
      treated with benazepril had better appetite (P = .017)
      as compared with those treated with placebo.
      Benazepril was well tolerated. In conclusion,
      benazepril decreased proteinuria in cats with CKD.

      ---
      Study related to benazepril and HCM - not terribly
      robust - not clear
      that heart changes were due to the drug (I do have a
      copy of this
      study if anyone would like one).

      Can Vet J. 2006 May;47(5):437-45. Links
      Benazepril and subclinical feline hypertrophic
      cardiomyopathy: a prospective, blinded, controlled
      study.

      Taillefer M, Di Fruscia R.
      Companion Animal Research Group, Small Animal
      Veterinary Teaching Hospital, Université de Montréal,
      3200, Sicotte Street, PO Box 5000, Saint-Hyacinthe,
      Quebec J2S 7C6. mylene.taillefer@...
      Twenty-one cats with hypertrophic cardiomyopathy were
      enrolled in this study to determine if the
      administration of benazepril (0.5 mg/kg body weight
      [BW], PO, q24h) to cats with subclinical hypertrophic
      cardiomyopathy improves cardiac diastolic function and
      reverses left ventricular hypertrophy when compared
      with diltiazem controlled delivery (CD) (10 mg/kg BW,
      PO, q24h). Cats were evaluated at day 0 and after 3
      and 6 months of therapy. In the benazepril group (n =
      11), the diastolic transmitral flow of the E and A
      waves ratio (E/A ratio) increased significantly
      between 0 and 6 months (P = 0.009) and the thickness
      of the left ventricular free wall in systole (LVFWs)
      decreased significantly between 0 and 3 months (P =
      0.04). In the diltiazem CD group (n = 5), none of the
      parameters varied significantly throughout the study.
      There was no difference between the benazepril and the
      diltiazem CD group throughout the study. Therefore,
      the variations observed for the E/A ratio and the
      LVFWs may have been incidental. Further studies will
      be needed to establish the role of benazepril in
      subclinical hypertrophic cardiomyopathy in cat.



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