Serum chloramphenicol concentrations in preruminant calves: a comparison of two formulations dosed orally

Serum concentrations of chloramphenicol were determined after oral doses (55 mg/kg body weight) were administered to 7–9 day old Holstein-Friesian calves. Chloramphenicol in an oral solution produced greater serum concentrations than did an equivalent dose of chloramphenicol in capsules ( P <0.005). A second dose of each formulation administered 12 h after the first dose elevated serum chloramphenicol concentrations significantly ( P <0.001). The average serum chloramphenicol concentration exceeded 5 μg/ml of serum 1 h after administration of the solution compared with 4 h for the capsules. Average serum chloramphenicol concentration was greater than 5 μg/ml for at least 12 h after the dose was administered for both formulations. Of the eight calves receiving repeat doses of chloramphenicol, seven (87.5%) developed diarrhea in 76 ± 8.6 h. Six of the eight calves (75%) died during or shortly after the period of chloramphenicol administration.     

Pharmacokinetics of chloramphenicol in the neonatal horse

Chloramphenicol sodium succinate was administered as an intravenous bolus (50 mg/kg) to eight foals which weighed 49–57 kg (mean ± 1 standard deviation = 53.19 ± 2.66) each, and were 1–9 days (4.5 ± 2.56) of age. The drug was rapidly distributed and followed first-order elimination. Mean pharmacokinetic values were: zero-time serum concentration (C₀) = 36.14 μg/ml (±14.80); apparent specific volume of distribution ( V_d ) = 1.614 1/kg (±0.669); and elimination rate constant ( K ) = 0.7295 h^-1 (±0.3066) which corresponds to a biological half-life ( t _1/2) = 0.95 h. These values do not differ greatly from those reported for adult horses and ponies.
A suspension of chloramphenicol was administered by nasogastric tube (50 mg/kg) to a second group of seven foals which weighed 49 to 57 kg (51.34 ± 2.82) each and were 1 to 7 days (4.43 ± 1.90) of age. A mean peak serum chloramphenicol concentration of 23.97 μg/ml (±7.06) was achieved 1.14h (±0.63) after administration. The bioavailability of this preparation was 83.27 percent.     

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a C_max= 0.61 ± 0.15 μg/ml, a T _max= 6 h and a t _½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values C_max= 1.55 ± 0.11 μg/ml, T _max= 8 h and 1 _max= 4.28 ± 0.18 h were obtained. For the higher dose C _max= 3.14 ± 0.04 μg/ml, T _max= 8 h and t _½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.     

Dose-sparing effects of romifidine premedication for thiopentone and halothane anaesthesia in the dog

Two intravenous doses of romifldine (40 and 80 μg/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifldine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 ± 3.6 mg/kg, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 6.5 ± 1.6 and 3.9 ± 0.3 mg/kg thiopentone, respectively.
Romlfldine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; piacebetreated dogs required 1.6 ± 0.3 per cent halothane, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 1.3 ± 0.4 and 0–8 ± 0.2 per cent, respectively.
Romifldine produced a significant shortening In the recovery from anaesthesia, and the higher dose of romlfldine significantly improved the overall quality of anaesthesia.     

Pharmacokinetics of valacyclovir in the adult horse

Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7–11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7–34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance liquid chromatography. Following the administration of 5 g VCV, the mean observed maximum serum ACV concentration ( C _max) was 1.45 ± 0.38 (SD) μg/mL, at 0.74 ± 0.43 h. At a dose of 15 g VCV, the mean C _max was 5.26 ± 2.82 μg/mL, at 1 ± 0.27 h. The mean bioavailability of ACV from oral VCV was 60 ± 12% after 5 g of VCV and 48 ± 12% after 15 g VCV, and did not differ significantly between dose rates ( P  > 0.05). Superposition suggested that a loading dose of 27 mg/kg VCV every 8 h for 2 days, followed by a maintenance dose of 18 mg/kg every 12 h, will maintain effective serum ACV concentrations.     

Pharmacokinetics of tobramycin in the camel

A/Hadi, A.A., Wasfi, I.A., Gadir, F.A., Amiri, M.H., Bashir, A.K. Baggot, J.D. Pharmacokinetics of tobramycin in the camel. J. vet. Pharmacol. Therap. 17 . 48–51.
The pharmacokinetics of tobramycin were determined in six healthy camels (Camelus dromedarius) following the intravenous (i.v.) and intramuscular (i.m. administration of single doses of tobramycin sulphate (40 mg/ml). The half-life to tobramycin was 189 ± 21 min and the mean residence time was 254 ± 26 min. The apparent volume of distribution (area method) was 245 ± 21 ml/kg. while volume of the central compartment of the two-compartment pharmaco-kinetic model was 110 ± 12 ml/kg. The clearance (systemic) of tobramycin was 0.90 ± 0.10 ml/min/kg. Values of the pharmacokinetic parameters suggest that glomerular filtration rate is lower in camels than in other ruminant species, horses, dogs and cats. Following i.m. administration of the dose (1.0 mg/kg), the drug was rapidly absorbed with peak serum concentration of 3.32 ± o.59 g/ml at 20–30 min; the absorption half-life was 3.9 ± 0.9 min. The systemic availability of tobramycin was 90.7 ± 14.4%. The apparent half-life was 201 ±40 min, which was not significantly longer than the half-life following i.v. administration of the drug. Based on the pharmacokinetic values obtained in this study, a dosing rate of 2.5 mg/kg administered by i.m. injection at 12-h intervals can be recommended. This dosage regimen should achieve an average steady state serum concentration of 4 g/ml with peak serum concentration approaching, but not exceeding, 10 g/ml.     

Diagnosis and treatment of pyogranulomatous panniculitis due to Mycobacterium smegmatis in cats

Four cats with extensive pyogranulomatous panniculitis and dermatitis due to Mycobacterium smegmatis were evaluated over an eight-month period. All were treated initially with doxycycline (50 mg per cat every eight to 12 hours) for several weeks, then subjected to radical surgical excision of infected tissues. Reconstructive surgery utilising advancement flaps was required to close wounds without undue tension. Postoperatively, the cats received parenteral gentamicin (2 mg/kg every eight hours) for three to five days, followed by orally administered ciprofloxacin (62.5 mg per cat every eight hours or 125 mg per cat every 12 hours) for three to six months. Infection was eradicated in all the cats, with no signs of recurrence 15 to 23 months after surgery.     

Pharmacokinetics of erythromycin in foals and in adult horses

The pharmacokinetic parameters of erythromycin in foals were determined following intravenous administration of 5.0 mg/kg to animals aged 1, 3, 5 and 7 weeks. The distribution of the drug was described by a two-compartment open model, and no significant differences were observed between coefficients on which the parameters were based. Pharmacokinetic values were also determined for four mares given 5.0 mg/kg intravenously and for six 10–12 week-old foals given 20.0 mg/kg intravenously. The half-life of erythromycin for all groups of animals (foals less than 7 weeks, mares, foals 10–12 weeks) was 1.0–1.1 h; the apparent volume of distribution was between 2.3 and 7.2 l/kg, and the clearance of the drug from the body was between 1.9 and 5.0 mg/kg/h. No drug could be detected in the serum following oral administration of 5.0 mg/kg erythromycin estolate; detectable levels were found for 5 h in mares given 12.5 mg/kg, and for 8 h in foals given 20.0 mg/kg orally. Peak levels in foals given the drug orally were 0.42 μg/ml at 120 min after administration. Foals given 10.0 mg/kg of erythromycin base intramuscularly had serum concentrations detectable 12 h later, the peak level achieved was 1.44 μg/ml serum 90 min after administration and concentrations exceeded 0.25 μg/ml for 6 h. In the mares the milk concentrations were approximately twice those in serum. Recommendations were made for drug dosage to be used in the treatment of Corynebacterium equi pneumonia of foals.     

Plasma and urine disposition and dose proportionality of ceftiofur and metabolites in dogs after subcutaneous administration of ceftiofur sodium

Nine male dogs (10.3–13.5 kg body weight) were randomly assigned to three groups of three dogs each and administered ceftiofur sodium subcutaneously as a single dose of 0.22, 2.2, or 4.4 mg ceftiofur free acid equivalents/kg body weight. Plasma and urine samples were collected serially for 72 h and assayed for ceftiofur and metabolites (derivatized to desfuroylceftiofur acetamide) using high-performance liquid chromatography. Urine concentrations remained above the MIC ₉₀ for Escherichia coll (4.0 μg/mL) and Proteus mirabilis (1.0 μg/mL) for over 24 h after doses of 2.2 mg/kg (8.1 μg/mL) and 4.4 mg/kg (29.6 μg/mL), the interval between treatments for ceftiofur sodium in dogs, whereas urine concentrations 24 h after dosing at 0.22 mg/kg (0.1 mg/Ib) were below the MIC ₉₀ for E.coli and P. mirabills (0.6 μg/mL). Plasma concentrations were dose-proportional, with peak concentrations of 1.66 ± 0.0990 μg/mL, 8.91 ± 6.42 μg/mL, and 26.7 ± 1.07 μg/mL after doses of 0.22, 2.2, and 4.4 mg/kg, respectively. The area under the plasma concentration versus time curve, when normalized to dose, was similar across all dosage groups.     

The susceptibility of isolates of Corynebacterium equi to antimicrobial drugs

Fifty-one isolates of Corynebacterium equi recovered from pigs and horses belonging to two capsular serotypes were tested for susceptibility to antimicrobial agents. No clear differences were detected in sensitivity between isolates of different sources or serotypes. All isolates were sensitive to <0.25 μg/ml of erythromycin and gentamicin. The following minimum inhibitory concentrations (MICs) of antimicrobial agents were determined for ≤90% of isolates: methicillin >16 μg/ml, clindamycin 1–2 μg/ml, tobramycin ≤1 μg/ml, cephalothin 8–64 μg/ml, kanamycin 2–8 μg/ml, amikacin ≤1–2 μg/ml, penicillin 2–≤4 μg/ml, ampicillin 2–8 μg/ml, trimethoprim-sulfa 4/76–32/608 μg/ml tetracycline 1–4 μg/ml and chloramphenicol 8–16 μg/ml.     

Systemic availability of chloramphenicol from tablets and capsules in cats

Five adult cats were given 100 mg chloramphenicol per os on five occasions: twice in tablet form, twice in capsules which also contained barium sulphate, and once in capsules without barium. Plasma samples for chloramphenicol assay were obtained on either a 'standard' schedule (four samples collected within 8 h of dosing with tablet, plain capsule or capsule including barium) or a 'frequent' schedule (nine samples collected within 8 h of dosing with tablet or capsule including barium). With frequent sampling, abdominal radiographs were taken at intervals after administration of capsules. No differences were found with the frequent schedule between tablet and capsule with regard to antibiotic concentrations at each sampling, peak concentrations, or area under the curve of plasma concentration versus time. Standard sampling gave similar drug concentrations to those obtained with frequent sampling. Delayed absorption (defined as plasma chloramphenicol concentration < 5 μg/ml for 1.5 h after dosing) occurred after six of the twenty-five administrations: it was not related to the frequency of sample collection or the use of capsules rather than tablets, but occurred mainly in certain cats. Poor absorption was shown radiographically in one cat to be associated with delayed dispersal of capsular contents in the gut.     

Clinical pharmacology of polymyxin B, colistin and colistimethate in young dairy calves

The in vitro sensitivity of 592 Gram-negative bacteria isolated from cattle against polymyxin B was determined by the agar plate dilution method. The minimal inhibitory concentration of polymyxin B for all but ten of the isolates was ≤ 2.0 μg/ml and 75% of the isolates were inhibited at 1.0 μg of polymyxin B/ml or less. Intramuscular injections of polymyxin B, colistin and colistimethate (CMS) were given to veal calves once daily for 3 days. Mean peak serum drug concentrations were observed within 0.5–1 h after treatment and were between 2.7 and 4.7 μg/ml when polymyxin B and colistin were administered at a dose rate of 2.5 mg/kg/day, and between 5.3 and 7.5 μg/ml at dose rate of 5.0 mg/kg/day. When CMS was given at 5.0 mg/kg/day mean peak drug concentration was 14.1 μg/ml. The elimination half-life ( t _1/2) of polymyxin B and colistin was 4–5 h but was approximately 2 h for CMS. Kidney function tests, using the double isotope single-injection method, were performed before and after the course of antibiotic treatment. No changes were detected in the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF) and blood urea levels were not raised following treatment. Several calves treated with the higher doses of polymyxin B and colistin exhibited transient ataxia and apathy 2–4 h after treatment but clinical signs suggesting interference with neurological function were not observed after an equivalent dose of CMS was administered.     

Clinical pharmacology of cefixime in unweaned calves

Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC₅₀) of field isolates of Escherichia coli. Salmonella and Pasteurella were 0.10–0.40 μg/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5–4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 μg/mL for the milk-fed calves and 1.76 μg/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC₅₀ of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.     

Ceftiofur hydrochloride: plasma and tissue distribution in swine following intramuscular administration at various doses

Twelve mixed-breed swine (26.5-42.5 kg) received three daily intramuscular (i.m.) doses of ¹⁴C-ceftiofur hydrochloride. Three males and three females, received 6.76 ± 0.83 mg of ¹⁴C-ceftiofur free acid equivalents (CFAE)/kg body weight (b.w.)/day, while the other group received 4.41 ± 0.97 mg-CFAE/kg b.w./day. The swine were slaughtered 12 h following the last dose. Total dose accountability for the 6.76 mg dose was 91.44 ± 16.11% (72.51% in urine; 12.63% in faeces). For the 4.41 mg dose, accountability was 100.35 ± 20.45% (82.48% in urine; 12.85% in faeces). Within the tissues used for residue monitoring, the highest concentrations were observed in the kidneys (10.68 and 6.33 μg-CFAE/g for the 6.76 and 4.41 mg doses, respectively), followed by the injection sites, lungs, liver and muscle. In a separate study, twelve mixbreed swine (23.1-39.7 kg) received ¹⁴C-ceftiofur hydrochloride at 3.08 mg-CFAE/kg b.w. once daily for 3 days. Two males and two females were slaughtered at either 12, 72 or 120 h after the last dose. Total dose accountability for the 3.08 mg dose was > 83% (> 68% in urine; > 13% in faeces). In swine slaughtered 12 h after the last dose, residue concentrations closest to the safe concentrations were observed in the kidneys (3.62 μg-CFAE/ g), followed by the injection sites, lungs, liver and muscle.     

A pharmacological study of chloramphenicol in Bubalus bubalis II*

The plasma levels of chloramphenicol were determined following i.m. administration in three groups of water buffalo (n= 4 per group). The absorption of chloramphenicol was relatively rapid since concentrations of 7.00 ± 0.62 μg/ml were detected in plasma after 1 h and peak concentrations of 9.25 ± 0.53 μg/ml were obtained 3 h following administration of 30 mg/kg. A concentration of at least 5 μg/ml was achieved at the end of 1 h and persisted up to 12 h (6.79 ± 1.19 μg/ml). With repetition of 10 and 20 mg/kg dose at 12 h, concentrations greater than 5 μg/ml persisted for an additional 8 and 12 h, respectively. The distribution studies of chloramphenicol in tissues and body fluids at 4 h post-injection (30 mg/kg i.m., n= 4, group IV), revealed that the highest concentration was seen in bile (31.67 ± 6.21 μg/ml), followed by liver, kidney, plasma, heart, skeletal muscle and brain (4.00 ± 0.50 μg/g).     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Comparison of three doses of dexmedetomidine with medetomidine in cats following intramuscular administration

Cats ( n  = 6) were administered dexmedetomidine (DEX) and medetomidine (MED) at three different dose levels in a randomized, blinded, cross-over study. DEX was administered at 25, 50 and 75 μg/kg (D25, D50 and D75), corresponding to MED 50, 100 and 150 μg/kg (M50, M100 and M150). Sedation, analgesia and muscular relaxation were scored subjectively. Heart and respiratory rates and rectal temperature were measured. Corresponding doses of DEX and MED were compared. Effects were also compared between dose levels for each compound. At dose level 2 (D50-M100), the duration of effective clinical sedation was significantly shorter after DEX (202.5±16.0 min) than after MED (230.0±41.2 min). Proceeding from D50-M100 to D75-M150, the duration of effective clinical sedation was increased more after DEX (by 57.5±38.4 min) than after MED (by 14.2±41.9 min) Increasing from D50-M100 to D75-M150, heart rate was further decreased after DEX (by 8.1±13.4%) but not after MED. There was no statistically significant difference between corresponding doses of DEX and MED for any of the other parameters studied. Changes in sedation, analgesia and muscular relaxation were dose-dependent. It was concluded that anaesthetic effects of medetomidine in cats are probably due entirely to its d-isomer and that dexmedetomidine at 25, 50 and 75 μg/kg induces dose-dependent sedation, analgesia and muscular relaxation of clinical significance in cats.     

Obligate anaerobes in clinical veterinary medicine: susceptibility to antimicrobial agents

Ninety-nine isolates of obligate anaerobic bacteria obtained from clinical material were tested for susceptibility to ten antimicrobial agents. Regardless of the species of animal from which the isolates were obtained 90–95% were inhibited by ≤4 μg of ampicillin/ml, ≤4 μg of chloramphenicol/ml, ≤1 μg clindamycin/ml, ≤2 μg metronidazole/ml, ≤8 μg minocycline/ml, ≤16 μg penicillin Gyml, and ≤16 μg tetracycline/ml. All the aminoglycoside antibiotics tested (gentamicin, kanamycin, neomycin, and streptomycin) were shown to be relatively ineffective requiring ≥128 μg/ml for the inhibition of >50%of the isolates. The minimal inhibitory concentration of penicillin G and tetracycline tended to be higher for isolates from non-human primates (penicillin G) and ruminants (tetracycline).     

Pharmacokinetics of kanamycin in dogs

The pharmacokinetics of kanamycin were studied in beagle dogs. A parenteral preparation of kanamycin sulphate (5% aqueous solution), which was given at a dosage level of 10 mg/kg of body weight, was the drug product used. The disposition curve which resulted from the intravenous administration of a single bolus dose of the drug was completely described by the biexponential equation:
C _p= 50e^{-0.1977 t} + 36.3e^{-0.0128 t} where C _p represents concentration of the drug in the serum at time t (in minutes) and the experimental constants are mean values. Pseudo-distribution equilibrium was rapidly attained and the apparent volumes of the central and peripheral compartments of the two-compartment open model were the same ( ca 125 ml/kg). Body clearance (mean ± S.D., n = 6) of kanamycin was 3.21 ±0.72 ml/kg/min. The half-life of the drug was short (58.18 ± 18.43 min) and independent of the route of parenteral (intravenous and intramuscular) administration. Absorption of kanamycin from the intramuscular site was rapid, with a half-time of 9.08 ± 1.10 min. A systemic availability of 89.1 ± 15.8% was obtained. Based on the bioavailability and disposition kinetics a dosage regimen consisting of the intramuscular injection of the dose (10 mg/kg) at 6 h intervals is proposed. An intravenous infusion rate of 48 μg/kgymin is predicted to establish a steady state serum concentration of 15 μg/ml, which is a therapeutic level of the antibiotic for susceptible micro-organisms.     

Amlodipine: A Randomized, Blinded Clinical Trial in 9 Cats with Systemic Hypertension

The efficacy of amlodipine (AML) was tested in hypertensive cats in a placebo-controlled, randomized, blinded clinical trial. Five cats were randomized to receive 0.625 mg AML once daily and 4 cats to receive placebo (PLA) once daily. The average systolic blood pressure (SBP) recorded by the Doppler method on day 0 was 212 ± 21 mm Hg in the AML group and 216 ± 32 mm Hg in the PLA group. On day 7, the cats receiving AML had a significantly lower average daily SBP (160 ± 30 mm Hg) but SBP in the PLA group was unchanged (207 ± 31 mm Hg). On day 7, all cats receiving PLA and one cat receiving AML were crossed over to the other group because of inadequate response. Blood pressure did not decrease adequately in 3 cats by day 14 (7 days of PLA and 7 days AML) and the treatment code was broken. Each of these cats was subsequently administered 1.25 mg AML daily. Cats requiring 1.25 mg AML once daily (6.1 kg ± 0.7 kg) weighed significantly more than cats that responded to 0.625 mg AML once daily (4.1 ± 0.7 kg). The average daily SBP recorded in the 6 cats that completed the study was significantly lower after 16 weeks of treatment (152 ± 14 mm Hg) compared to day 0 (221 ± 24 mm Hg). Three cats were euthanized before completion of the study. All 3 cats were responders to AML on day 7. SBPs measured 24 hours after AML administration were similar to the average daily SBP, suggesting that AML effectively controlled SBP for a 24-hour period. AML was shown to be an effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 ± 0.03 mg/kg sid.