Drug therapy during pregnancy and in the neonate

This article presents important clinical pharmacologic aspects of drug therapy during pregnancy. It reviews the potential adverse effects on the mother and conceptus caused by drugs and includes specific recommendations for therapy. Extensive tables are included that list drugs that are safe and those that are contraindicated during pregnancy.     

Antimicrobial therapy for gastrointestinal diseases.

Antibiotics will always be needed in horses for many types of infections, but the adverse consequences also must be considered. For the conditions described in this article, there is justification for antibiotic therapy. The intestinal problems that antibiotics can induce are among the risks from their administration to horses. Disruption of the endogenous bacterial population, colitis, and diarrhea are the most common complications from antibiotic therapy.     

Recovery of brodifacoum in vomitus following induction of emesis in dogs that had ingested rodenticide bait

AIM: To assess the benefit of inducing emesis in dogs that have ingested rodenticide bait containing brodifacoum (BDF), by determining the amount of BDF in bait recovered from the vomitus relative to the estimated amount consumed.

METHODS: Between 2014 and 2015 samples of vomitus from seven dogs that ingested rodenticide baits containing BDF were submitted by veterinarians in New Zealand. All seven dogs had been given apomorphine by the veterinarian and vomited within 1 hour of ingesting the bait. Some or all of the bait particles were retrieved from each sample and were analysed for concentrations of BDF using HPLC. Based on estimations of the mass of bait consumed, the concentration of BDF stated on the product label, and the estimated mass of bait in the vomitus of each dog, the amount of BDF in the vomited bait was calculated as a percentage of the amount ingested.

RESULTS: For five dogs an estimation of the mass of bait ingested was provided by the submitting veterinarian. For these dogs the estimated percentage of BDF in the bait retrieved from the vomitus was between 10–77%. All dogs were well after discharge but only one dog returned for further testing. This dog had a normal prothrombin time 3 days after ingestion.

CONCLUSIONS AND CLINICAL RELEVANCE: The induction of emesis within 1 hour of ingestion can be a useful tool in reducing the exposure of dogs to a toxic dose of BDF. The BDF was not fully absorbed within 1 hour of ingestion suggesting that the early induction of emesis can remove bait containing BDF before it can be fully absorbed.     

Retrospective assessment of tolerability and efficacy of zoledronate in the palliative treatment of cancer-bearing dogs

Zoledronate is a bisphosphonate frequently used for the treatment of hypercalcaemia of malignancy and tumour-associated bone pain in dogs, however, there is a paucity of information regarding its use in veterinary medicine. The aim of this retrospective study was to report the tolerability of zoledronate in the palliative treatment of cancer-bearing dogs and secondarily to to assess the efficacy of zoledronate for the treatment of hypercalcaemia of malignancy. Thirty-seven dogs (22 with tumour-associated bone pain and 15 with hypercalcaemia of malignancy) that received 114 zoledronate infusions were included. Tolerability was assessed by the absence of post-zoledronate hypocalcaemia or other adverse events as defined by Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events criteria. Efficacy was assessed by comparison of available ionized calcium levels before and after zoledronate administration in hypercalcaemic dogs. In 79% of zoledronate infusions, no adverse events were reported. The majority of adverse events which occurred in the other 21% of infusions could be attributed to concurrent chemotherapy or the underlying neoplastic disease. There was a small but significant increase in creatinine following treatment with zoledronate, however, none of the dogs developed clinically significant renal disease. In eight hypercalcaemic dogs with available ionized calcium following zoledronate administration, ionized calcium decreased rapidly within 7 days following treatment with zoledronate. Zoledronate is well-tolerated with few recorded adverse events, however, monitoring of serum creatinine is advised. Zoledronate seems to be effective in the treatment of hypercalcaemia of malignancy.     

Comparison of plasma and interstitial fluid concentrations of doxycycline and meropenem following constant rate intravenous infusion in dogs

OBJECTIVE: To compare plasma (total and unbound) and interstitial fluid (ISF) concentrations of doxycycline and meropenem in dogs following constant rate IV infusion of each drug. ANIMAL: 6 adult Beagles. PROCEDURE: Dogs were given a loading dose of doxycycline and meropenem followed by a constant rate IV infusion of each drug to maintain an 8-hour steady state concentration. Interstitial fluid was collected with an ultrafiltration device. Plasma and ISF were analyzed by high performance liquid chromatography. Protein binding and lipophilicity were determined. Plasma data were analyzed by use of compartmental methods. RESULTS: Compared with meropenem, doxycycline had higher protein binding (11.87% [previously published value] vs 91.75 +/- 0.63%) and lipophilicity (partition coefficients, 0.02 +/- 0.01 vs 0.68 +/- 0.05). A significant difference was found between ISF and plasma total doxycycline concentrations. No significant difference was found between ISF and plasma unbound doxycycline concentrations. Concentrations of meropenem in ISF and plasma (total and unbound) were similar. Plasma half-life, volume of distribution, and clearance were 4.56 +/- 0.57 hours, 0.65 +/- 0.82 L/kg, and 1.66 +/- 2.21 mL/min/kg, respectively, for doxycycline and 0.73 +/- 0.07 hours, 0.34 +/- 0.06 L/kg, and 5.65 +/- 2.76 mL/min/kg, respectively, for meropenem. The ISF half-life of doxycycline and meropenem was 4.94 +/- 0.67 and 2.31 +/- 0.36 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The extent of protein binding determines distribution of doxycycline and meropenem into ISF. As a result of high protein binding, ISF doxycycline concentrations are lower than plasma total doxycycline concentrations. Concentrations of meropenem in ISF can be predicted from plasma total meropenem concentrations.     

Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep

OBJECTIVE: To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. ANIMALS: 5 mature Katahdin ewes weighing 42 to 50 kg. PROCEDURE: Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 microg/ml, respectively. Median Cmax of the multiple-dose regimen was 2.99 microg/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC < or = 0.29 microg/ml.     

Pharmacokinetics of ketoprofen in the green iguana (Iguana iguana) following single intravenous and intramuscular injections.

The nonsteroidal antiinflammatory drug ketoprofen (KTP) is a commonly used antiinflammatory and analgesic agent in reptile medicine, but no studies documenting its pharmacokinetics in this species have been published. Ketoprofen was administered as a racemic mixture to green iguanas (Iguana iguana) intravenously (i.v.) and intramuscularly (i.m.) at 2 mg/kg. Pharmacokinetic analyses were performed and indicated that ketoprofen in iguanas administered by the intravenous route has a classical two-compartmental distribution pattern, a slow clearance (67 ml/ kg/hr) and a long terminal half-life (31 hr) compared to ketoprofen studies reported in mammals. When delivered by the intramuscular route, bioavailability was 78%. These data indicate the daily dosing that is generally recommended for reptile patients, as an extrapolation from mammalian data, may be more frequent than necessary.     

Single-dose intravenous and oral pharmacokinetics of enrofloxacin in goral (Nemorrhaedus goral arnouxianus).

This study describes the pharmacokinetics of enrofloxacin following oral and i.v. administration to goral (Nemorrhaedus goral arnouxianus). The objective of this study was to expand upon current antimicrobial treatment options available for use in goral by measuring plasma concentrations and examining the pharmacokinetics of enrofloxacin in these animals. Two single-dose treatments of enrofloxacin were administered to four goral in a crossover design. Single-dose treatments consisted of administration of injectable enrofloxacin i.v. (5 mg/kg) and enrofloxacin tablets (136 mg chewable tablets) dissolved in a grain slurry and administered p.o. (10 mg/kg). Plasma levels of enrofloxacin and its metabolite ciprofloxacin were measured with the use of high-performance liquid chromatography with UV detection. Plasma volume of distribution for i.v. enrofloxacin was 2.15 - 1.01 L/kg, with a mean elimination half-life of 13.3 hr and total body clearance of 0.19+/-0.14 L/kg/hr. The maximum plasma concentration measured for oral enrofloxacin was 2.77 microg/ml, with a mean half-life of 5.2 hr and systemic availability of 14.6%. The area under the plasma concentration over time curve (AUC) for oral enrofloxacin was 21.06 microg/hr/ml. The area under the plasma concentration over time curve generated for oral enrofloxacin in goral yields an area under the plasma concentration over time curve to minimum inhibitory concentration ratio > 100 for many gram-positive and gram-negative bacterial pathogens common to small ruminants. Based on these results, oral enrofloxacin may be considered for further study as a treatment option for susceptible infections in goral.