Pharmacokinetics of amikacin after intravenous, intra-articular, and combined intravenous and intra-articular administration in healthy neonatal foals.

BACKGROUND: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration. HYPOTHESIS/OBJECTIVES: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. ANIMALS: Eight healthy neonatal foals. METHODS: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 µg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. RESULTS: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean µg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.

Time- and temperature-dependent postmortem ∆9-tetrahydrocannabinol concentration changes in rabbits following controlled inhaled cannabis administration.

ostmortem redistribution (PMR), a well-known phenomenon in forensic toxicology, can result in substantial changes in drug concentrations after death, depending on the chemical characteristics of the drug, blood collection site, storage conditions of the body and postmortem interval (PMI). Limited PMR data are available for ∆9-tetrahydrocannabinol (THC), the primary psychoactive component in Cannabis sativa. PMR was evaluated after controlled cannabis inhalation via a smoking machine and exposure chamber in New Zealand white rabbits. Necropsies were performed on five control rabbits immediately after euthanasia, whereas 27 others were stored at room temperature (21°C) or refrigerated conditions (4°C) until necropsy at 2, 6, 16, 24 or 36 h after death. THC and its Phase I and glucuronidated Phase II metabolites were quantified in blood, vitreous humor, urine, bile and tissues by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Under refrigerated temperature, heart blood THC concentrations significantly increased at PMI 2 h in rabbits, whereas peripheral blood THC concentrations showed a significant increase at PMI 16 h. Central:peripheral blood and liver:peripheral blood ratios for THC ranged from 0.13 to 4.1 and 0.28 to 8.9, respectively. Lung revealed the highest THC concentrations, while brain and liver exhibited the most stable THC concentrations over time. This report contributes much needed data to our understanding of postmortem THC behavior and can aid toxicologists in the interpretation of THC concentrations in medicolegal death investigations.

Pharmacokinetics of ponazuril after administration of a single oral dose to green turtles (Chelonia mydas).

The coccidian protozoan, Caryospora cheloniae, has been associated with severe enteritis and encephalitis in immature farm-raised green turtles (Chelonia mydas) in the Cayman Islands, immature green turtles off the coast of Florida, and immature stranded sea turtles in Australia. An effective anti-coccidial drug that is both orally absorbed and well-distributed throughout the body is needed for treatment of turtles diagnosed with coccidiosis in rehabilitation facilities. Ponazuril is a triazine antiprotozoal drug that is approved in the USA for the treatment of another Apicomplexan, Sarcocystis neurona, and has also been successfully used in the therapy of other coccidian parasites. The objective of this study was to perform an oral dose-ranging pilot study (10-100 mg/kg of body weight ponazuril) in green turtles (N = 9), followed by oral administration of ponazuril at 100 mg/kg body weight (N = 8) to assess its disposition. Another goal of this study was to optimize the method of oral drug administration to green turtles. Plasma ponazuril concentrations were quantified using high performance liquid chromatography (HPLC). Standard compartmental models were fit to the data. Ponazuril was absorbed after oral administration at 100 mg/kg BW, with a maximum plasma concentration of 3.3 µg/ml. Dose-dependent pharmacokinetic parameters only weakly correlated with the dose rate, apparently due to considerable pharmacokinetic variability observed between turtles. Administration of ponazuril in gelatin capsules using a balling gun was deemed the least variable and most successful method of drug administration. Further studies are needed to evaluate the safety and efficacy of ponazuril in sea turtles with coccidiosis.

Effective Prophylactic Therapy for Exposure to Monkey B Virus (Macacine alphaherpesvirus 1).

Zoonotic monkey B virus (Macacine alphaherpesvirus 1; BV) infections are extremely serious and usually fatal. Drugs currently used for treatment were developed for the treatment of herpes simplex virus but are less effective against BV. Effective suppression of viral replication in the skin could prevent the virus from invading the nervous system. To test this hypothesis, the efficacy of topical administration of several drugs against lethal BV infection was evaluated in female BALB/c mice that were infected by scarification. Drugs were then applied to the site of inoculation. As 3% preparations, most drugs were only minimally effective or ineffective. In contrast, ganciclovir and cidofovir were very effective. The ED50 for cidofovir was 0.007%, compared with 1.1% for ganciclovir. At 0.5%, cidofovir protected against both death and neurologic signs, whereas 5% ganciclovir only protected against death but not neurologic involvement. All genotypes of BV were equally susceptible to cidofovir and ganciclovir. For maximal effectiveness, treatment with both cidofovir and ganciclovir had to be initiated within 8 h of infection. Cidofovir was completely protective when administered only on the day of infection, whereas a minimum of 5 d of treatment was required for maximal ganciclovir efficacy. These studies showed that topical cidofovir treatment started soon after BV exposure was very effective in preventing BV from invading the nervous system, whereas ganciclovir treatment was only partially effective. In addition, cidofovir was protective against a ganciclovir-resistant BV mutant, whereas ganciclovir was not. These studies showed that topical cidofovir treatment started soon after BV exposure is more effective than ganciclovir in preventing BV from invading the CNS.

Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular pulmonary fibrosis.

BACKGROUND: Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. OBJECTIVES: To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. ANIMALS: Six horses diagnosed with EMPF. METHODS: A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 20 mg/kg). Blood, NS, and BALF were collected for EHV-5 viral kinetics analyses during treatment. Blood and NS were collected every other day. BALF was collected on day 0 and day 10. RESULTS: There was no statistical difference in median EHV-5 viral load between day 0 and day 10 for all samples tested. In blood median EHV-5 viral load was 7676 (range 575-39 781) on day 0 and 6822 (range 1136-18 635) glycoprotein B (gB) gene copies per million cells on day 10. For NS median EHV-5 viral load was 2.944 × 106 (range 184 691-3.394 × 109 ) on day 0 and 8.803 × 106 (range 251 186-9.868 × 108 ) gB gene copies per million cells on day 10. For BALF median EHV-5 viral load was 59,842 (range 61-315 655) on day 0 and 185 083 (range 3562-542 417) gB gene copies per million cells on day 10. CONCLUSIONS AND CLINICAL IMPORTANCE: Valacyclovir might not be an effective short-term antiviral treatment but efficacy in treatment of EMPF is unknown.

Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-1 infection in horses.

OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 µg/mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1-infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.

Antiherpetic Drugs in Equine Medicine.

Since vaccination may not prevent disease, antiherpetic drugs have been investigated for the therapy of several equine herpesviruses. Drug efficacy has been assessed in horses with disease, but most evidence is in vitro, in other species, or empirical. Oral valacyclovir is most often administered in the therapy of equine herpesvirus type-1 (EHV-1) to protect adult horses from equine herpesvirus myeloencephalopathy, while oral acyclovir is frequently administered for EHV-5 infection in the therapy of equine multinodular pulmonary fibrosis. Other antiherpetic drugs are promising but require further investigation. Several topical drugs are also empirically used in the therapy of equine viral keratitis.

Comparison of Glucosamine Absorption After Administration of Oral Liquid, Chewable, and Tablet Formulations to Dogs.

Glucosamine (GS) is commonly administered as a nutritional supplement to support joint function. Although many supplements are available, the effect of formulation on oral absorption in dogs is unknown. The purpose of this study was to determine the relative bioavailability of GS for liquid, chewable, and tablet formulations containing GS sulfate or hydrochloride and chondroitin sulfate. In a randomized cross-over design, supplements were administered daily for 8 days with a 1 wk washout period between treatments. Liquid or Tablet A was administered to four dogs, whereas Liquid or Tablet B was administered to four additional dogs. When nutraceutical exposure was normalized to the administered dose of GS free base, similar relative bioavailabilities were determined for all three formulations. However, the dose-normalized maximum plasma GS concentration was higher for the liquid supplement (5.5 ± 0.5 µg/mL) than for the two tablets (3.1 ± 0.6 and 2.1 ± 0.6 µg/mL, P < 0.001). Similarly, the time at which maximal plasma GS concentrations occurred was shorter for the liquid formulation (0.7 ± 0.5 hr) than for the two tablets (4.2 ± 0.6 and 5.0 ± 0.6 hr, P < 0.001). These data show that the formulation of joint supplements affects the oral absorption of GS in dogs.

Papiine herpesvirus 2 as a predictive model for drug sensitivity of Macacine herpesvirus 1 (monkey B virus).

Monkey B virus (Macacine herpesvirus 1; BV) is endemic in macaques. BV (a BSL4 agent) is the primary zoonotic concern for persons working with macaques in research, and human BV infections frequently are fatal. We assessed the use of a BSL2 baboon herpesvirus (Papiine herpesvirus 1; HVP2) for predicting the drug sensitivity of BV by comparing the sensitivity of the 2 viruses to 12 antiherpetic drugs. Plaque reduction assays showed that 4 drugs (HBPG, BVdU, PFA, and BrdU) were ineffective against both viruses. Of the 8 effective drugs, both viruses were most sensitive to TFT, whereas sensitivity to the remaining 7 drugs varied between BV and HVP2 as well as between strains of HVP2. In addition, the efficacy of 5 drugs (ACV, PCV, GCV, CDV, and EDU) was tested by using a murine model. ACV and EDU were completely ineffective against both HVP2 and BV, and high doses of PCV only delayed death by a few days. GCV and CDV both protected mice against death, and CDV also prevented the development of neurologic symptoms. When the initiation of drug therapy was delayed until after virus gained access to the CNS, both GCV and CDV were ineffective. The similarity of the drug sensitivities of HVP2 and BV in both models validates the use of HVP2 as a BSL2 level model that can be used to predict drug sensitivity of BV. The greater efficacy of CDV relative to GCV suggests the potential for use of CDV in the treatment of zoonotic BV infections.

Simultaneous quantification of vinblastine and desacetylvinblastine concentrations in canine plasma and urine samples using LC-APCI-MS/MS.

A highly sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS/MS) method has been developed and validated for simultaneous quantification of vinblastine and its metabolite, desacetylvinblastine, in canine plasma and urine samples. Plasma and urine samples were processed by a solid phase extraction procedure. The optimal chromatographic behavior of these analytes was achieved on pentafluorophenyl (PFP) propyl analytical column (5µm, 50×2.1mm) under isocratic elution of 0.75mL/min with a mobile phase of 5mM ammonium acetate and methanol. The samples were analyzed in positive ion, multiple reaction monitoring mode. The calibration curves were linear over 0.125-2ng/mL (lower calibration curve); 2-100ng/mL (higher calibration curve) and 0.125-5ng/mL for vinblastine and desacetylvinblastine in plasma, and over 1-2000ng/mL and 0.5-100ng/mL for vinblastine and desacetylvinblastine in urine samples, respectively. The limits of quantitation of vinblastine and desacetylvinblastine were 0.125ng/mL in both matrices. The intra and interday accuracy was above 89% and precision below 8.6% for both analytes in both matrices. The developed method was successfully applied to ongoing in vivo vinblastine pharmacokinetic studies in dogs.

Pharmacokinetics of tetracycline after single-dose oral administration in the American alligator (Alligator mississippiensis).

The major objective of the study was to assess the pharmacokinetics of tetracycline administered orally to fasted and nonfasted American alligators (Alligator mississippiensis) at 50 mg/kg. Plasma levels of tetracycline were determined using high-performance liquid chromatography with ultraviolet detection. The concentration versus time curve was analyzed using a compartmental modeling technique. A one-compartment model with first-order absorption and elimination, as well as a lag time to absorption, best described the data. The area under the curve and mean residence time values differed significantly between the fasted and nonfasted groups. Based on the results of this study, tetracycline suspension administered once orally at 50 mg/kg to American alligators is not expected to reach plasma concentrations above the breakpoint minimum inhibitory concentration of 4 microg/ml for susceptible organisms.

Fecal egg counts after anthelmintic administration to aged horses and horses with pituitary pars intermedia dysfunction.

OBJECTIVE: To determine effects of pituitary pars intermedia dysfunction (Cushing's disease) and age on fecal egg count and time to egg reappearance after anthelmintic treatment in horses residing in similar environments. DESIGN: Cross-sectional study. ANIMALS: 29 healthy horses (4 to 35 years old) and 13 horses with PPID (13 to 33 years old). PROCEDURES: Fecal egg counts were performed by use of a modified Wisconsin flotation method at 2-week intervals before and after ivermectin treatment. RESULTS: Horses with PPID had higher fecal egg counts before and 8, 10, and 12 weeks after ivermectin treatment, compared with counts for site-matched healthy horses. There was no difference in the period for < 90% reduction in fecal egg counts between the 2 groups. Age did not affect fecal egg counts at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: For similar environmental conditions, horses with PPID were more likely to have higher fecal egg counts than were healthy horses. Therefore, horses with PPID may need to have a more aggressive parasite prevention program than do healthy horses. Age did not affect fecal egg counts or time to egg reappearance after anthelmintic treatment, which suggested age alone does not likely require special consideration when designing a parasite control program for adult horses.

Use of propofol-xylazine and the Anderson Sling Suspension System for recovery of horses from desflurane anesthesia.

OBJECTIVE: To characterize the behavior of horses recovering in the Anderson Sling Suspension System after 4 hours of desflurane anesthesia and postdesflurane intravenous (IV) administration of propofol and xylazine. STUDY DESIGN: Experimental study. ANIMALS: Healthy horses (n=6), mean+/-SEM age 12.3+/-1.8 years; mean weight 556+/-27 kg. METHODS: Each horse was anesthetized with xylazine, diazepam, and ketamine IV and anesthesia was maintained with desflurane in O(2). At the end of 4 hours of desflurane, each horse was positioned in the sling suspension system and administered propofol-xylazine IV. Recovery events were quantitatively and qualitatively assessed. Venous blood was obtained before and after anesthesia for biochemical and propofol analyses. RESULTS: Anesthetic induction and maintenance were without incident. Apnea commonly accompanied propofol administration. All horses had consistent recovery behavior characterized by a smooth, careful, atraumatic return to a standing posture. CONCLUSIONS: Results of this study support careful, selective clinical use of desflurane, propofol-xylazine, and the Anderson Sling Suspension System to atraumatically transition horses with high anesthetic recovery risk to a wakeful standing posture. CLINICAL RELEVANCE: Technique choices to facilitate individualized, atraumatic recovery of horses from general anesthesia are desirable. Use of IV propofol and xylazine to transition horses from desflurane anesthesia during sling recovery to standing posture may facilitate improved recovery management of high-injury risk equine patients requiring general anesthesia.

Effect of administration of propofol and xylazine hydrochloride on recovery of horses after four hours of anesthesia with desflurane.

OBJECTIVE: To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). PROCEDURES: Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration. RESULTS: Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.

Characterization of a spontaneous drug-resistant mutant of monkey B virus (Macacine herpesvirus 1).

Monkey B virus (Macacine herpesvirus 1; BV) is an alpha-herpesvirus of macaques that causes serious infections in humans. A spontaneous mutant resistant to penciclovir (PCV) was isolated. Several genes were sequenced to identify mutations potentially responsible for PCV resistance. A single nucleotide deletion in the thymidine kinase (TK) gene was identified. To confirm its role in PCV resistance, several TK recombinants were constructed. A TK-deletion virus and a recombinant carrying the mutation were both resistant to PCV, while a revertant was PCV-sensitive. These results demonstrate that spontaneous drug-resistant mutants of BV do occur and that the BV TK is responsible for sensitivity to PCV.

Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.

Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.

Effect of fentanyl on visceral and somatic nociception in conscious horses.

BACKGROUND: Transdermal fentanyl is used clinically in horses based on pharmacokinetic data and antinociceptive effects documented in other species. HYPOTHESIS: Fentanyl IV administration increases both visceral and somatic nociceptive threshold in conscious horses. ANIMALS: Six clinically normal horses, each fitted with a permanent gastric cannula. METHODS: Visceral nociception was evaluated with 2 methods of threshold detection--olorectal distention and duodenal distention. Somatic nociception was assessed by measurement of thermal threshold. Fentanyl was administered as an increasing stepwise infusion followed by a continuous-rate infusion for a total of 2 hours. There were 4 doses of fentanyl and 1 dose each of saline and xylazine administered to each horse. Serum fentanyl concentrations were measured and the resulting data were used to determine pharmacokinetic parameters for each horse. All data were analyzed by means of a 3-factor analysis of variance followed by either a simple t test or a Bonferroni t test for multiple comparisons. RESULTS: Fentanyl administration did not result in significant changes in duodenal or colorectal distention threshold. Thermal threshold showed an increased trend at the 15-minute time point for the highest fentanyl group only, with a corresponding mean serum fentanyl concentration of 7.82 +/- 2.10 ng/mL. Two horses in this group became agitated and tachycardic during the first 15 minutes of the infusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Fentanyl did not produce a significant antinociceptive effect at the doses used, 2 of which resulted in serum concentrations above the nociceptive threshold in other species.

Terbutaline pharmacokinetics in cows: preliminary data.

The objective of this study was to determine the serum pharmacokinetics of terbutaline in healthy cows. In the initial experiment, terbutaline was administered once as an intravenous (i.v.) bolus to 6 near-term pregnant beef cows within 24 h after parturition at a low but therapeutically relevant dose, 5 microg/kg. A 2nd experiment was conducted in the same cows with a higher dose, 0.5 mg/kg, but an otherwise similar experimental design. The serum concentration of terbutaline was determined by means of high-performance liquid chromatography with fluorescence detection in both experiments. After i.v. administration of 0.5 mg/kg, the mean peak serum concentration, residence time, and half-life were 708.22 (standard deviation 509.6) ng/mL, 6.75 (3.6) min, and 6.93 (2.4) min, respectively. The results indicate that terbutaline is rapidly eliminated from the bloodstream after i.v. administration in cattle, falling below the assay's limit of detection 30 min after administration.

Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after oral and intravenous administration of pentoxifylline to healthy adult horses.

OBJECTIVE: To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses. ANIMALS: 8 healthy adult horses. PROCEDURES: A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV administration. For oral administration, blood samples were collected 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 hours after the last dose. RESULTS: Elimination of pentoxifylline was rapid after IV administration. After oral administration, pentoxifylline was rapidly absorbed and variably eliminated. Higher serum concentrations of pentoxifylline and apparent bioavailability were observed after oral administration of the first dose, compared with values after administration of the last dose on day 8 of treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, oral administration of 10 mg of pentoxifylline/kg results in serum concentrations equivalent to those observed for therapeutic doses of pentoxifylline in humans. Twice daily administration appears to be appropriate. However, serum concentrations of pentoxifylline appear to decrease with repeated dosing; thus, practitioners may consider increasing the dosage if clinical response diminishes with repeated administration.

Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses.

The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.