Antibody and T cell responses induced in chickens immunized with avian influenza virus N1 and NP DNA vaccine with chicken IL-15 and IL-18

We had examined the immunogenicity of a series of plasmid DNAs which include neuraminidase (NA) and nucleoprotein (NP) genes from avian influenza virus (AIV). The interleukin-15 (IL-15) and interleukin-18 (IL-18) as genetic adjuvants were used for immunization in combination with the N1 and NP AIV genes. In the first trial, 8 groups of chickens were established with 10 specific-pathogen-free (SPF) chickens per group while, in the second trial 7 SPF chickens per group were used. The overall N1 enzyme-linked immunosorbent assay (ELISA) titer in chickens immunized with the pDis/N1 + pDis/IL-15 was higher compared to the chickens immunized with the pDis/N1 and this suggesting that chicken IL-15 could play a role in enhancing the humoral immune response. Besides that, the chickens that were immunized at 14-day-old (Trial 2) showed a higher N1 antibody titer compared to the chickens that were immunized at 1-day-old (Trial 1). Despite the delayed in NP antibody responses, the chickens co-administrated with IL-15 were able to induce earlier and higher antibody response compared to the pDis/NP and pDis/NP + pDis/IL-18 inoculated groups. The pDis/N1 + pDis/IL-15 inoculated chickens also induced higher CD8+ T cells increase than the pDis/N1 group in both trials (P < 0.05). The flow cytometry results from both trials demonstrated that the pDis/N1 + pDis/IL-18 groups were able to induce CD4+ T cells higher than the pDis/N1 group (P < 0.05). Meanwhile, pDis/N1 + pDis/IL-18 group was able to induce CD8+ T cells higher than the pDis/N1 group (P < 0.05) in Trial 2 only. In the present study, pDis/NP was not significant (P > 0.05) in inducing CD4+ and CD8+ T cells when co-administered with the pDis/IL-18 in both trials in comparison to the pDis/NP. Our data suggest that the pDis/N1 + pDis/IL-15 combination has the potential to be used as a DNA vaccine against AIV in chickens.     

The use of eugenol against Aeromonas hydrophila and its effect on hematological and immunological parameters in silver catfish (Rhamdia quelen)

The aim of this study was to evaluate the activity of eugenol against the fish pathogen Aeromonas hydrophila and eugenol's effect on hematological and natural immune parameters in silver catfish (Rhamdia quelen). In vitro, eugenol showed weak activity against A. hydrophila, but in vivo, at a subinhibitory concentration (10 mg L^?1), it promoted survival in infected silver catfish. Eugenol (50 μg mL^?1) reduced the hemolytic activity of A. hydrophila supernatant in vitro in fish erythrocytes. Subjecting catfish to eugenol baths (5 and 10 mg L^?1) for five days did not alter the hematological and immunological parameters studied in this work. Based on these results, eugenol can be used to treat or prevent bacterial diseases in fish.     

Pharmacokinetics,plasma protein binding and bioavailability of moxifloxacin in Muscovy ducks after different routes of administration

In this study the disposition kinetics and plasma availability of moxifloxacin in Muscovy ducks after single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of 5 mg kg^?1 b.wt. were investigated. The concentrations of moxifloxacin in the plasma were measured using high-performance liquid chromatography (HPLC) with fluorescence detection on samples collected at frequent intervals after drug administration. Following intravenous injection, the decline in plasma drug concentration was bi-exponential with half-lives of (t_1/2α) 0.22 ± 0.10 h and (t_1/2β) 2.49 ± 0.26 h for distribution and elimination phases, respectively. The volume of distribution at steady-state (V_dss) was 1.02 ± 0.14 l kg^?1 and the total body clearance (Cl_tot) was 0.32 ± 0.11 l kg^?1 h^?1, respectively. After intramuscular and oral administration of moxifloxacin at the same dose the peak plasma concentrations (C_max) were 2.38 ± 0.43 and 2.11 ± 0.36 μg ml^?1 and were obtained at 1.47 ± 0.26 and 1.83 ± 0.16 h (T_max), respectively, the elimination half-lives (T_1/2el) were 3.14 ± 0.42 and 2.63 ± 0.44 h, respectively, and AUC_0–24 were 15.87 ± 2.35 and 14.52 ± 2.37 μg ml^?1 h^?1, respectively. The systemic bioavailabilities were 96.36 ± 11.54% and 86.79 ± 12.64%, respectively. In vitro plasma protein binding percent was 32%. We concluded that moxifloxacin might be clinically interesting alternative for the treatment of most sensitive bacterial infections in Muscovy ducks.     

Enhancement of humoral and cellular immunity in mice against Japanese encephalitis virus using a DNA prime–protein boost vaccine strategy

A synthetic multi-epitope gene containing critical epitopes of the Japanese encephalitis virus (JEV) envelope gene was cloned into both prokaryotic and eukaryotic expression vectors. The recombinant plasmid and purified recombinant protein (heterologously expressed in Escherichia coli) were used as immunogens in a mouse model. The results indicate that both the recombinant protein and the DNA vaccine induce humoral and cellular immune responses. Neutralising antibody titres in mice in the pcDNA-TEP plus rEP group increased considerably relative to mice immunised using either pcDNA-TEP or rEP alone (P < 0.05). Furthermore, the highest levels of interleukin (IL)-2, interferon-γ and IL-4 were induced following priming with the DNA vaccine and boosting with the recombinant protein. Together these findings demonstrate that a DNA-recombinant protein prime-boost vaccination strategy can produce high levels of antibody and trigger significant T cell responses in mice, highlighting the potential value of such an approach in the prevention of JEV infection.     

Supplementing Guinea grass with fresh sweet potato foliage for milk production by Bunaji and N'Dama cows in early lactation

Forage from three sweet potato cultivars (A = TIS-87/0087; B = TIS-8164; C = TIS-2532.OP.1.13 at 30% daily dry matter intake), dried brewers' grains (DBG) and cottonseed meal (CSM) each at 2.5 kg were supplemented to Guinea grass (GG) to form four diets: Diet A = GG + TIS-87/0087; Diet B = GG + TIS-8164; Diet C = GG + TIS-2532.OP.1.13, and Diet D = GG + DBG + CSM (as control). Treatments were assigned as 4 × 4 Latin squares design over 60 days (10-day adaptation and 5-day sampling) using Bunaji and N'Dama cows in early lactation. The 48-h rumen dry matter (DM) degradation ranged (P < 0.01) from 407 g kg^? 1 DM for GG to 791 g kg^? 1 DM for sweet potato cultivar TIS-87/0087. Bunaji dry matter intake varied (P < 0.05) between 7.1 kg day^? 1 in Diet B and 8.9 kg day^? 1 in Diet D, but was similar (P > 0.05) among diets for the N'Dama cows. The metabolisable energy (ME) intakes were higher for Diet D although, it recorded the least efficiency of ME utilization for milk production. Milk yields were significantly (P < 0.01) higher in the Bunaji than the N'Dama cows, which is typical of their true breed differences. Total solids, ash, protein, fat, and sugar contents of the milk were similar among diets for both cow breeds, except Bunaji ash contents that ranged (P < 0.05) from 0.77 g 100 g^? 1 for Diet B to 0.83 g 100 g^? 1 for Diet D. The results suggest that sweet potato forage could be utilized as whole or partial replacement for DBG and CSM to save cost under smallholder farming systems.     

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs

To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg^?1) as a positive control, followed by TDB (52.5 μg h^?1) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL^?1 (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1 h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect.     

Vaccination with a genotype 1 modified live vaccine against porcine reproductive and respiratory syndrome virus significantly reduces viremia,viral shedding and transmission of the virus in a quasi-natural experimental model

The present study assessed the efficacy of vaccination against genotype 1 porcine reproductive and respiratory syndrome virus (PRRSV) in terms of reduction of the transmission. Ninety-eight 3-week-old piglets were divided in two groups: V (n = 40) and NV (n = 58) that were housed separately. V animals were vaccinated with a commercial genotype 1 PRRSV vaccine while NV were kept as controls. On day 35 post-vaccination, 14 NV pigs were separated and inoculated intranasally with 2 ml of a heterologous genotype 1 PRRSV isolate (“seeder” pigs, SP). The other V and NV animals were distributed in groups of 5 pigs each. Two days later, one SP was introduced into each pen to expose V and NV to PRRSV. Sentinel pigs were allocated in adjacent pens. Follow-up was of 21 days. All NV (30/30) became viremic after contact with SP while only 53% of V pigs were detected so (21/40, p < 0.05). Vaccination shortened viremia (12.2 ± 4 versus 3.7 ± 3.4 days in NV and V pigs, respectively, p < 0.01). The 50% survival time for becoming infected (Kaplan–Meier) for V was 21 days (CI_95% = 14.1–27.9) compared to 7 days (CI_95% = 5.2–8.7) for NV animals (p < 0.01). These differences were reflected in the R value as well: 2.78 (CI_95% = 2.13–3.43) for NV and 0.53 (CI_95% = 0.19–0.76) for V pigs (p < 0.05). All sentinel pigs (10/10) in pens adjacent to NV + SP pens got infected compared to 1/4 sentinel pigs allocated contiguous to a V + SP pen. These data show that vaccination of piglets significantly decrease parameters related to PRRSV transmission.     

Experimental infection of Artibeus intermedius with a vampire bat rabies virus

Experimental infection of Artibeus intermedius, the great fruit-eating bat, was performed with vampire bat rabies isolates. Bats (n = 35) were captured in the wild and quarantined prior to experimental infection. No rabies antibodies were detected by rapid fluorescent focus inhibition test (RFFIT) prior to infection. Three doses of rabies virus (RV) and three different routes of infection were used. One out of 35 bats died without showing any clinical signs at day 14 and was positive for rabies. None of the 34 other bats showed clinical signs for rabies, but high antibody titers were detected post-inoculation, suggesting either innate immune response to the vampire bat rabies virus or possible pre-exposure to RV and inoculation leading to a booster effect. Rabies virus was detected by hemi-nested RT-PCR (hnRT-PCR) in the brain (n = 3), stomach (n = 1) of bats that were negative by immunofluorescence and that survived rabies infection. The bat that died on day 14 was positive by hnRT-PCR on the brain, heart and liver. These results suggest that either previous non-lethal exposure to RV or natural low susceptibility to vampire bat viruses somehow protected Artibeus intermedius from clinical rabies infection leading to a marginal lethality effect on this bats species population in the wild.     

Resveratrol decreases oxidative burst capacity and alters stimulated leukocyte cytokine production in vitro

IntroductionResveratrol, a naturally-occurring phytophenol, has been shown to bolster immune surveillance and reverse immunosenescence in a dose dependent manner in rodents and humans. Although safety and pharmacokinetic studies have been completed in dogs, the immunomodulatory effects of resveratrol in dogs has not yet been investigated. The objective of this study was to determine the effect of resveratrol on canine innate immune system function in vitro. The hypothesis was that similar to other species, low concentrations of resveratrol would stimulate while high concentrations would depress innate immune system function.MethodsWhole blood was collected from six healthy, adult, client-owned dogs and was incubated with resveratrol at final concentrations of 6000 ng ml⁻¹, 3000 ng ml⁻¹, 1000 ng ml⁻¹, or control solution for 4 h. Following incubation, phagocytosis and oxidative burst were evaluated using flow cytometry, and LPS-, lipoteichoic acid (LTA) – and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay.ResultsPhagocytosis was not altered by resveratrol at any concentration compared to control. However, while the number of PMNs capable of performing oxidative burst did not change, the robustness of the reaction following stimulation with Escherichia coli and PMA was reduced in a dose dependent manner. In addition, LPS-, LTA-, PG, and PBS-stimulated TNF production was increased following incubation with all concentrations of resveratrol compared to control, and this effect was dose dependent. LTA-stimulated IL-6 was increased with resveratrol compared to control. Furthermore, LTA-stimulated IL-10 was decreased with 6000 ng ml⁻¹ and 3000 ng ml⁻¹ concentrations of resveratrol and PG-stimulated IL-10 production was decreased with all concentrations of resveratrol compared to control. The LPS-, LTA-, and PG-stimulated TNF:IL-10 ratio was increased with 6000 ng ml⁻¹ of resveratrol compared to control and lower resveratrol concentrations.ConclusionWhile resveratrol was sparing to PMN phagocytosis, it reduced the robustness of PMN oxidative burst. Resveratrol also increased pro-inflammatory and decreased anti-inflammatory leukocyte cytokine production capacity in vitro. These data suggest that resveratrol supplementation may depress oxidative burst reactions while promoting pro-inflammatory leukocyte cytokine production and decreasing anti-inflammatory cytokine production. Based on these findings, further in vivo study regarding the effects of resveratrol on PMN oxidative burst capability and leukocyte cytokine production capacity are indicated prior to routine supplementation.     

Modelling the lactation curve of rabbit does: Towards a model including fit suitability and biological interpretation

This work proposes an adequate empirical model for the 28-day lactation curve of rabbit does, including fit suitability and biological interpretation. A total of 15,400 test-day milk records were used, corresponding to 550 lactations collected from 134 hybrid New Zealand × Californian rabbit does during five consecutive lactations. To develop this model, five different functions were compared (quadratic, potential, beta-modified, gamma and Gauss models), evaluating their fitting ability to mean and individual lactation curves, and the suitability of their parameters to gather the sources of variation (genetic selection level, type of diet, parity order and gestation overlapping degree) on lactation curve shape. The possible relationship between model parameters and main performance traits was also evaluated. From the results of the present work, it may be concluded that beta-modified equation [Milk yield (g/day) = k × (day/30)^a × (1 −  (day/30))^b] could be proposed as an alternative to quadratic models for daily milk yield prediction of reproductive rabbit does. When compared to quadratic models, beta-modified model give a slightly better fit to average (R² = 0.986 vs. 0.985; RMSE = 5.648 vs. 5.813) and individual (Residuals = 21.31 vs. 21.37 g; Mean square prediction error = 883.0 vs. 897.2 g²) lactation curves, especially of those curves showing a lower lactation peak height and a greater persistence of milk yield. However, the most important advantage of the beta-modified model was the greater biological interpretation of its parameters (k regulates the curve height, while a and b regulate the milk yield of ascending and descending period, respectively) and the ability to gather curve changes. This latter aspect is revealed by the relationship of the parameters with main performance traits of lactating does (energy intake, live weight and body reserves mobilisation). Although further research on developing an optimal model is needed, the use of this type of models could provide additional information for a better understanding of the curve shape effect on the performance, body condition and health of reproductive rabbit does.     

Evaluation of long-term antibody responses to two inactivated bovine viral diarrhoea virus (BVDV) vaccines

The aim of the present study was to determine the serological response of heifers after vaccination with two inactivated bovine viral diarrhoea virus (BVDV) vaccines by means of various ELISA tests. Three dairy farms were selected from the Galicia region of Spain. In each herd, a batch of heifers to be vaccinated for the first time was selected and followed for 15 months. Heifers from farm 1 (n = 25) were vaccinated with Vaccine A, whereas heifers from farm 2 (n = 16) were vaccinated with Vaccine B. Heifers from farm 3 (n = 17), where no BVDV vaccines were used, acted as controls. Blood samples were analyzed periodically for BVDV antibodies, using five commercial ELISAs, based on BVDV p80 antigen or whole virus.At the end of the study, none of the animals vaccinated with Vaccine A seroconverted according to p80 antibody status, whereas up to 80% tested positive by ELISA against whole virus antigen. For the animals vaccinated with Vaccine B, 2/16 animals seroconverted according to p80 antibody ELISAs, whereas all had seroconverted according to the ELISA against whole virus antigen. In most cases, based on the use of ELISAs to detect specific antibodies against the p80 protein, at 15 months post-vaccination with inactivated BVDV vaccines the responses did not seem to interfere with detection of antibody to BVDV infection. However, the finding of a small proportion of vaccinated animals seropositive against BVDV p80 antigen suggests that antibodies that interfere with diagnosis of BVDV infection within the herd could exist, even when using p80 ELISAs.     

The effect of sea transport from Ireland to the Lebanon on inflammatory,adrenocortical, metabolic and behavioural responses of bulls

The objective was to investigate the effect of sea transport on the physiological, behavioural and performance responses of bulls. One-hundred and eleven bulls (mean body weight (standard error of the mean) 429 (5.7 kg)) were randomly assigned to one of three treatments; control (C; n = 54) bulls were housed in 6 pens at Teagasc, Grange Research Centre at a stocking density of (1), 1.7 m²/head (C1.7; 3 pens) and (2), 3.4 m²/head (C3.4; 3 pens) and (3), transported (T) bulls (n = 57) were penned at a space allowance of 1.7 m²/head (6 pens) and allocated to one of five decks on the shipping vessel. C and T bulls were subjected to the same live weight (d −2), blood sampling and rectal temperature (d −1) measurements pre-transport and on d 3, d 6, d 9 and d 11 of the study. T bulls had greater (P < 0.05) live weight gain (+4.4%) compared with C1.7 bulls (−2.0%) and C3.4 (+0.13%)). Time spent lying was greater (P < 0.05) among C1.7 and C3.4 bulls (9.9% and 53.3%, respectively) compared with T bulls (45.8%). Rectal body temperature was not different (P > 0.05) among treatment groups throughout the study. At d 11, neutrophil % was greater (P < 0.05) in transported bulls on decks 1, 2, 4 and 5 compared with C1.7 and C3.4 treatments. Plasma cortisol concentrations were not different (P > 0.05) between control and transported bulls. Plasma creatine kinase (CK) activity was lower (P < 0.05) among C3.4 and T bulls on decks 2, 3, 4 and 5 compared with d 3 values. In conclusion, the welfare of bulls transported by sea on the sea journey was not adversely affected. Housing control bulls at a reduced space allowance (1.7 m²) had a negative effect on live weight gain.     

Pharmacokinetic,metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid–liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t_1/2α) of 0.50 ± 0.07 h, elimination half-life (t_1/2β) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l⁻¹. The volume of distribution at steady state (Vd_ss) 1.92 ± 0.22 l kg⁻¹, volume of the central compartment of the two compartment pharmacokinetic model (V_c) 0.87 ± 0.09 l kg⁻¹, and total body clearance (Cl_T) of 0.60 ± 0.09 l/h kg⁻¹. Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350 mg orphenadrine aspartate.     

Systemic and local immune response in pigs intradermally and intramuscularly injected with inactivated Mycoplasma hyopneumoniae vaccines

The systemic and respiratory local immune response induced by the intradermal administration of a commercial inactivated Mycoplasma hyopneumoniae whole-cell vaccine (Porcilis^® MHYO ID ONCE – MSD AH) in comparison with two commercial vaccines administered via the intramuscular route and a negative control (adjuvant only) was investigated. Forty conventional M. hyopneumoniae-free pigs were randomly assigned to four groups (ten animals each): Group A = intradermal administration of the test vaccine by using the needle-less IDAL^® vaccinator at a dose of 0.2 ml; Group B = intramuscular administration of a commercially available vaccine (vaccine B); Group C = intramuscular administration of the adjuvant only (2 ml of X-solve adjuvant); Group D = intramuscular administration of a commercially available vaccine (vaccine D). Pigs were vaccinated at 28 days of age. Blood and bronchoalveolar lavage (BAL) fluid samples were collected at vaccination (blood only), 4 and 8 weeks post-vaccination. Serum and BAL fluid were tested for the presence of antibodies by ELISA test. Peripheral blood monomorphonuclear cells (PBMC) were isolated to quantify the number of IFN-γ secreting cells by ELISpot. Moreover, cytokine gene expression from the BAL fluid was performed. Total antibodies against M. hyopneumoniae and specific IgG were detected in serum of intradermally and intramuscularly (vaccine B only) vaccinated pigs at 4 and 8 weeks post-vaccination. M. hyopneumoniae specific IgA were detected in BAL fluid from vaccinated animals (Groups A and B) but not from controls and animals vaccinated with the bacterin D (p < 0.05). Significantly higher gene expression of IL-10 was observed in the BAL fluid at week 8 post-vaccination in the intradermally vaccinated pigs (p < 0.05). The results support that the intradermal administration of an adjuvanted bacterin induces both systemic and mucosal immune responses. Moreover, the intramuscularly administered commercial vaccines each had a different ability to stimulate the immune response both systemically and locally.     

A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis

Currently there are no effective vaccines for the control of bovine neosporosis. During the last years several subunit vaccines based on immunodominant antigens and other proteins involved in adhesion, invasion and intracellular proliferation of Neospora caninum have been evaluated as targets for vaccine development in experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and the immunodominant NcGRA7 protein have been assessed with varying results. Recent studies have shown that another rhoptry component, NcROP40, and NcNTPase, a putative dense granule antigen, exhibit higher expression levels in tachyzoites of virulent N. caninum isolates, suggesting that these could be potential vaccine candidates to limit the effects of infection. In the present work, the safety and efficacy of these recombinant antigens formulated in Quil-A adjuvant as monovalent vaccines or pair-wise combinations (rNcROP40 + rNcROP2 and rNcGRA7 + rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All the vaccine formulations elicited a specific immune response against their respective native proteins after immunization. Mice vaccinated with rNcROP40 and rNcROP2 alone or in combination produced the highest levels of IFN-γ and exhibited low parasite burdens and low IgG antibody levels after the challenge. In addition, most of the vaccine formulations were able to increase the median survival time in the offspring. However, pup survival only ensued in the groups vaccinated with rNcROP40 + rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly, vertical transmission was not observed in those survivor pups immunized with rNcROP40 + rNcROP2, as shown by PCR analyses. These results show a partial protection against N. caninum infection after vaccination with rNcROP40 + rNcROP2, suggesting a synergistic effect of the two recombinant rhoptry antigens.     

Pharmacokinetics of erythromycin after intravenous,intramuscular and oral administration to cats

The aim of this study was to characterise the pharmacokinetic properties of different formulations of erythromycin in cats. Erythromycin was administered as lactobionate (4 mg/kg intravenously (IV)), base (10 mg/kg, intramuscularly (IM)) and ethylsuccinate tablets or suspension (15 mg/kg orally (PO)). After IV administration, the major pharmacokinetic parameters were (mean ± SD): area under the curve (AUC)_(0–∞) 2.61 ± 1.52 μg h/mL; volume of distribution (V_z) 2.34 ± 1.76 L/kg; total body clearance (Cl_t) 2.10 ± 1.37 L/h kg; elimination half-life (t_½λ) 0.75 ± 0.09 h and mean residence time (MRT) 0.88 ± 0.13 h. After IM administration, the principal pharmacokinetic parameters were (mean ± DS): peak concentration (C_max), 3.54 ± 2.16 μg/mL; time of peak (T_max), 1.22 ± 0.67 h; t_½λ, 1.94 ± 0.21 h and MRT, 3.50 ± 0.82 h. The administration of erythromycin ethylsuccinate (tablets and suspension) did not result in measurable serum concentrations. After IM and IV administrations, erythromycin serum concentrations were above minimum inhibitory concentration (MIC)₉₀ = 0.5 μg/mL for 7 and 1.5 h, respectively. However, these results should be interpreted cautiously since tissue erythromycin concentrations have not been measured and can reach much higher concentrations than in blood, which may be associated with enhanced clinical efficacy.