Héctor Sumano

The use of lidocaine-sodium bicarbonate as anaesthetic in fish

Abstract Lidocaine and lidocaine-sodium bicarbonate mixture were evaluated as anaesthetics for carp ( Cyprinus carpio ), catfish ( Ictalurus punctatus ) and tilapia ( Tilapia mossambica = Oreochromis mossambicus ). Although both induced anaesthesia, the mixture was more effective for induction and recovery, and was able to achieve the required time for the fish to be out of water. The responses varied for the three test species.

Enrofloxacin hydro-chloride dihydrate.

The asymmetric unit of the title compound, C19H23FN3O3 +·Cl−·2H2O [systematic name: 4-(3-carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinolin-7-yl)-1-ethylpiperazin-1-ium chloride dihydrate], consists of two independent monocations of the protonated enrofloxacin, two chloride anions and four water molecules. In the cations, the piperazinium rings adopt chair conformations and the dihedral angles between the cyclopropyl ring and the 10-membered quinoline ring system are 56.55 (2) and 51.11 (2)°. An intramolecular O—H⋯O hydrogen bond is observed in each cation. In the crystal, the components are connected via O—H⋯Cl, N—H⋯Cl and O—H⋯O hydrogen bonds, and a π–π interaction between the benzene rings [centroid–centroid distance = 3.6726 (13) Å], resulting in a three-dimensional array.

Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses

BackgroundDoxycyline (Dox) is a semisynthetic antibacterial drug with pharmacological advantages over its parent drug (tetracycline) in the treatment of various bacterial diseases in horses. Yet, at present a horse-customized pharmaceutical formulation is not available. Based on its pharmacokinetic/pharmacodynamic (PK/PD) ratio, Dox is considered a time-dependent antibacterial drug and ideally expected to achieve sustained plasma drug concentrations both at or slightly above the minimal inhibitory concentration (MIC) level for as long as possible between dosing intervals. Hence, the objective of this study was to formulate two long-acting (LA) doxycyline hyclate (Dox-h) formulations for oral administration and define their pharmacokinetics in non-fasted adult horses to obtain better bioavailability and longer mean residence time, features needed to comply better with its pharmacokinetic/pharmacodynamic (PK/PD) ratios.ResultsPharmacokinetic parameters were determined after the oral administration of a single 10 mg/kg bolus dose of two 20% Dox-h formulations: one based on a β cyclodextrin (Dox-β) matrix and a second one on a poloxamer (Dox-pol) matrix. The results were compared with the pharmacokinetics of a single 10 mg/kg bolus oral dose of a freshly made aqueous Dox-h solution (Dox-a). Dox-pol showed the greatest values for relative bioavailability (548%); maximum serum concentration (Cmax) value was 1.3 ± 0.7 μg/mL with time to reach the Cmax (Tmax) of 5.9 ± 1.7 h, area under the curve (AUC) of 17.0 ± 2.2 μg h/ml and elimination half-life (T½ β) of 4.9 ± 1.0 h.ConclusionsConsidering a minimal inhibitory concentration MIC of 0.25 μg/mL, clinically effective plasma concentrations might be obtained for up to 24 h administering Dox-pol. This is an oral paste formulation that might optimize the use of Dox-h in horses in terms of PK/PD ratio congruency, and it is likely that it may also improve prescription compliance due to its ease of administration.

Serum and tissue concentrations of doxycycline in broilers after the sub-cutaneous injection of a long-acting formulation

1. The antibacterial agent doxycycline hyclate (Dox) is usually administered to broilers in drinking water or as a feed supplement. Parenteral injection is not the usual route for administration, so a long-acting formulation (Dox-LA) was tested to evaluate if serum concentrations can achieve the pharmacokinetic/pharmacodynamic (PK/PD) ratios regarded as adequate for the drug. 2. A poloxamer-based matrix was used to provide Dox-LA. Serum and tissue concentrations of Dox vs time were determined in two day-old broilers after subcutaneous (SC) injection of Dox-LA or oral administration of a single bolus of aqueous Dox (Dox-PO), at a dose of 20 mg/kg. Weight gain, feed conversion rate, haematological variables, aspartate aminotransferase and alanine aminotransferase activities, blood urea and creatinine were determined and compared for Dox-LA with Dox-PO and non-medicated controls. 3. Dox-LA had a high relative bioavailability (1200%). Maximum serum concentrations were not statistically different (5·1 ± 1·1 µg/ml for Dox-LA and 6·1 ± 1.4 µg/ml for Dox-PO), but half-life of Dox-LA was much greater than the value obtained for Dox-PO (73·0 ± 0·9 h and 2·0 ± 0·02 h, respectively). Tissue concentrations were higher, and stayed higher for longer periods in the Dox-LA group. 4. In conclusion, considering the minimum effective serum concentration against Mycoplasma spp is 0·5 µg/ml, a dose-interval of 180 h can be achieved with Dox-LA, but only for 24 h after Dox-PO. Better PK/PD ratios for Dox-LA should result in improved clinical outcomes compared with Dox-PO.

Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs.

Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases.

Pharmacokinetics of disodium fosfomycin in broilers and dose strategies to comply with its pharmacodynamics versus Escherichia coli

The objective of this study was to determine, in broilers, which modality of disodium fosfomycin (DF) administration and at what dose the best pharmacokinetic (PK) profile could be obtained, taking as reference a 110 field bacterial strains of Escherichia coli minimum inhibitory concentration survey. The DF was administered via drinking water either ad libitum or at a higher concentration having 1 h of water restriction to build up thirst in the birds (loading dose). Dosages tested were 10, 20, 40, and 80 mg/kg per administration, either once or twice daily. Birds included were 24-d-old Cornish broilers randomly assigned to 16 groups of 200 birds per group and 3 replicates per group. The PK of DF was determined after ad libitum administration of either a single- or double-loading dose or after an initial loading dose followed by ad libitum medication. Also, PK after i.v. administration was studied in separate groups. Serial blood samplings were performed in all groups. Serum obtained was analyzed for DF and a possible active metabolite by means of a microbiological agar diffusion assay. The DF showed a short elimination half-life (approximately 2 h after oral loading administration) with a rapid clearance (1.23 to 1.42 mL/kg per h). Apparent volume of distribution-area under the curve values were also low (10 and 80 mg/kg=0.25 L/kg and 0.22 L/kg, respectively). Considering a minimum inhibitory concentration level that inhibited 90% of total strains of 8 µg/mL for E. coli, it is concluded that single-loading administration at 10, 20, 40, and 80 mg/kg complies poorly with sustained serum concentrations over a dosing interval of 24 h. Doses of 10 and 20 mg/kg twice a day also were insufficient to attain therapeutic concentrations. Useful serum concentrations of DF to treat outbreaks of susceptible E. coli require an initial loading dose of 40 mg/kg, followed by an ad libitum medication of 40 mg/kg 8 h later (80 mg/kg per d).

Plasma concentrations resulting from florfenicol preparations given to pigs in their drinking water1

Florfenicol administered through the drinking water has been recommended as a metaphylactic antibacterial drug to control outbreaks of respiratory diseases in pigs caused by strains of Actinobacillus pleuropneumoniae and Pasteurella multocida, yet it is difficult to pinpoint in practice when the drug is given metaphylactically or therapeutically. Further, pigs are likely to reject florfenicol-medicated water, and plasma concentrations of the drug are likely to be marginal for diseases caused by Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The reported minimal inhibitory concentration (MIC) values for these organisms show a breakpoint of 2 to 3 μg/mL. An experiment was conducted during September and October 2009. One hundred twenty healthy crossbred pigs (Landrace-Yorkshire), weighing 23 ± 6.2 kg, were used in this trial. They were randomly assigned to 5 groups, with 3 replicates of 8 animals/group. Two commercial preparations of florfenicol were administered through the drinking water at 2 concentrations (0.01 and 0.015%). Water intake was measured before and after medication, and plasma concentrations of florfenicol were determined by HPLC. Considerable rejection of florfenicol-medicated water was observed. However, plasma florfenicol concentrations were of a range sufficient for a methaphylaxis approach to preventing disease by bacteria, with MIC breakpoints of ≤ 0.25 μg/mL. Decreased efficacy as a metaphylactic medication should be expected for bacteria with MIC >0.25 μg/mL, considering the reported existence of bacteria resistant to florfenicol and the natural resistance of Streptococcus suis or E. coli to this drug.

Pharmacokinetics after administration of an injectable experimental long-acting parenteral formulation of doxycycline hyclate in goats.

OBJECTIVE To determine the pharmacokinetics after SC administration of an experimental, long-acting parenteral formulation of doxycycline hyclate in a poloxamer-based matrix and after IV and IM administration of an aqueous formulation of doxycycline hyclate in goats. ANIMALS 30 clinically normal adult goats. PROCEDURES Goats were allocated to 3 groups (10 goats/group). One group of goats received doxycycline hyclate (10 mg/kg) IM, a second group received the same dosage of doxycycline hyclate IV, and the third group received the long-acting parenteral formulation of doxycycline hyclate SC. Serum concentrations of doxycycline were determined before and at various intervals after administration. RESULTS The long-acting parenteral formulation of doxycycline hyclate had the greatest bioavailability (545%); mean +/- SD maximum serum concentration was 2.4 +/- 0.95 microg/mL, peak time to maximum concentration was 19.23 +/- 2.03 hours, and elimination half-life was 40.92 +/- 4.25 hours. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the long-acting parenteral formulation of doxycycline hyclate distributed quickly and widely throughout the body after a single dose administered SC, and there was a prolonged half-life. Bioavailability of the longacting parenteral formulation of doxycycline hyclate after SC administration was excellent, compared with bioavailability after IV and IM administration of an aqueous formulation of doxycycline hyclate. Although no local tissue irritation and adverse effects were detected, clinical assessment of drug-residues and toxicologic evaluations are warranted before this long-acting parenteral formulation of doxycycline hyclate can be considered for use in goats with bacterial infections.

Successful treatment of canine open cervix-pyometra with Yun-Nan-Pai-Yao, A chinese herbal preparation

Pyometra is a relatively common disease in bitches. It has been estimated that approximately 4–5% of all bitches will suffer from this disease during their lives (Noakes et al., 2001). Concisely, pyometra can be defined as an intrauterine collection of cell debris (pus) possibly due to an exacerbated influence of progesterone (Noakes et al., 2001). To date, surgical intervention by means of ovariohysterectomy is recommended if the patient’s clinical condition is critical, if there is no requirement for further breeding, if prevention of development of cystic endomentrial hyperplasia is necessary, and complete cure must be ensured (Memon and Mickelsen, 1993). Alternatively, an injection of prostaglandin F2α has been described (Brown, 1985). Adverse drug reactions include vocalization, panting, grooming, tenesmus, restlessness, salivation, diarrhoea, kneading, mydriasis, emesis, urination and defecation. Reactions begin as soon as 30 s after administration of F2α . These side-effects are transient and resolve within 60 min after subcutaneous injection. Moreover, the side-effects become less severe with subsequent injections or when lower dosages are given more frequently (Delverdier et al., 1984). Other treatments include application of the anti-progestin aglepristone. This is the first antiprogestin registered for veterinary use with the indication ‘interruption or prevention of pregnancy’, but it has been successfully used for induction of parturition in the dog and cat, and for the conservative treatment of pyometra in the dog (Hofmann and Schuler, 2002). Other treatments that have been described, such as antibiotic therapy (pefloxacin tablets 4 mg/kg b.i.d.), dinoprost (a synthetic prostaglandin related to F2α) 200 μg/kg subcutaneously once daily, and daily deep vaginal douches with 200 ml warm 1% povidone-iodine) (Pawde and Kumar, 1996), have not achieved wide acceptance by the medical community. Although anti-progestin therapy has been well accepted by the medical community in Europe, it is our belief that improvements can be made. Traditional Chinese medicine (TCM) has proved to be a source of new ideas for the treatment of various diseases in humans and animals. This medical approach has a reputation

Acaricidal Action of Water Extracts from Eysenhardtia polystachya Against Rhipicephalus (Boophilus) microplus

ABSTRACT: The action of a water extract of Eysenhardtia polystachya on the cattle tick Rhipicephalus (Boophilus) microplus adults and larvae was studied. A stock solution of the extract was serially diluted in distilled, sterile water to obtain test concentrations of 1%, 0.5%, 0.25%, 0.125%, and 0.0625%, and a field trial was carried out on Cebu/Holstein F1 cattle experimentally infected with ticks. The extract was applied by spraying at a rate of 5 liters per animal per day for 7 d. The effectiveness of treatment against engorged females was assessed by measuring mortality and egg production in an adult immersion test. Although the natural extract was found to be nonlethal to adults, it had a significant effect on egg-laying at the highest concentrations, inhibiting 64.58% of oviposition. Using a larval immersion test, the extract was determined to be highly toxic to the larvae at the higher concentrations, killing 100, 99.94 ± 0.06, 99.35 ± 0.37, 99.17 ± 0.14, and 99.03 ± 0.01 at concentrations of 1%, 0.5%, 0.25%, 0.125%, and 0.0625%, respectively, after 72 hr of immersion. Field trial results also revealed nonadulticidal efficacy. Nevertheless, adult ticks and egg masses recovered from treated calves weighed less than those collected from untreated controls. Also, daily application of the plant extract over 7 d provided 94.82% control as measured by the index of fecundity in engorged females. Aqueous extract from E. polystachya possesses a well-defined acaricidal effect on R. microplus larvae and inhibits oviposition. These findings allow us to suggest that further extraction and characterization of the active compound(s) responsible for the observed acaricidal activity may reveal new xenobiotics for further drug-development and can contribute to our understanding of the larvacidal mechanism of action of E. polystachya extract.