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Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep.

ABSTRACT: Plasma pharmacokinetic profiles and the anti-inflammatory efficacy of meloxicam were determined when administered subcutaneously (SC) or intramuscularly (IM) to sheep. Merino ewes were initially injected with 0.1 mL of oil of turpentine into a forelimb to induce inflammation, followed by either 1.0 mg/kg or 2.0 mg/kg of meloxicam administered either SC or IM (n = 6 per treatment group) or followed by no meloxicam administration (control) (n = 4). Ewes were examined to determine skin temperature, limb circumference, limb sensitivity and signs of lameness at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 48 h following treatment, with blood collected at these time-points to quantify meloxicam plasma concentrations. Skin temperature of ewes dosed with meloxicam at 1.0 mg/kg SC and 2.0 mg/kg IM at 12 h and 1.0 mg/kg SC at 24 were significantly different to the controls (P < 0.05). Limb circumferences of ewes dosed with 1.0 mg/kg IM were significantly different to controls at 10 h and 12 h (P < 0.05). All meloxicam treatment groups resulted in reduced limb sensitivity compared to controls at 6 h, with the 1.0 and 2.0 mg/kg IM treatments significantly different at 12 h (P < 0.05) and 1.0 and 2.0 mg/kg SC groups, significantly different to controls at 48 h (P < 0.05). No significant difference in lameness scores were detected over 48 h. The 1.0 mg/kg IM treatment had a significantly greater plasma meloxicam concentration than the 1.0 mg/kg SC treatment over 0.5 to 4 h (P < 0.001). Both 1.0 mg/kg SC and IM treatments demonstrated elimination half-lives (mean ± SD) of 10.82 ± 2.46 and 12.63 ± 2.37 h, respectively. Meloxicam at all doses provided some anti-inflammatory and analgesic effects from 6 to 48 h; however no route could be distinguished as more efficacious than the others.

SUBMITTER: Woodland AN

PROVIDER: S-EPMC6481916 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn patients treated with oral anticoagulants, subcutaneous injections of anti-tetanus vaccine are usually recommended to reduce the risk of bleeding, although the effectiveness of the vaccine has only been proven for intramuscular injection. The objective of this study was to compare the safety and efficacy of intramuscular and subcutaneous injections of tetanus-diphtheria vaccine in patients treated with oral anticoagulants.Methods/designWe present a prospective, double blinded, clinical trial comparing two groups of patients with oral anticoagulants: one group was administered tetanus-diphtheria vaccine by intramuscular injection, while the other was administered the same vaccine by subcutaneous injection. Allocation to each group was randomized and the duration of the study was six years.Study populationall patients treated with oral anticoagulants, who had been administered with at least one dose of vaccine, at 15 Health Centres in Vigo (Spain), and who agreed to participate in the study. The sample size was 115 patients in each group. The main variables for the safety analysis were the measurement of the brachial diameter, the appearance of basic injuries at the vaccine administration site, the appearance of pain and systemic reactions. The variable used for the efficacy analysis was a significant increase in the titres of anti-tetanus toxoid antibodies.An Intention-to-treat analysis will be performed. Details will be classified according to the administration route, while within each group a 3-tiered stratification will be defined by the administered number of doses. As a measure of association, relative risk will be estimated; the reduction of relative risk will also measured. For safety and to control the confounder effect, a logistic regression analysis will be carried out. As a measure of impact the reduction of absolute risk in relation to the total number of patients to be treated and the Number Needed to Treat will be estimated.CONSORT 2010 guidelines were applied for reporting parallel group randomised trials.DiscussionThe most significant difficulties on the project are related to the large number of participating centres, required to obtain a viable study population sample size, and the coordination given the scattering of the centres and researchers.Trial registrationISRCTN69942081.

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Project description:Background and objectivesA multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG) given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID), is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK.Materials and methods50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years.ResultsStage 1, 85% of the subjects aged >12 years and 93% of the subjects aged <12 years achieved IgG levels ≥6 and ≥4 g/L, respectively at all observations. There were 3.62 infections/patient/year during Subgam treatment. The most common product-related events were infusion site reactions (50% of patients). Recent post-hoc pharmacokinetics analysis of the post-infusion serum total IgG concentration indicated that the mean dose-normalised incremental IgG AUCτ following intravenous dosing (120.5 g.day/L) was 1.64-fold that of the dose-normalised mean incremental IgG AUCτ following subcutaneous dosing (73.6 g.day/L), corresponding to an estimated IgG bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse reactions have been received in 30 patients over a period of 10 years; fourteen were classed as serious as defined by the ICH guidelines on good clinical practice. The most common post-licensing adverse reaction was infusion site reaction (7 reports). There were 7 reports of flu-like symptoms (pyrexia/shivering/rigors/feeling hot or cold), 2 other reports of combined flu-like symptoms and infusion site reactions, 5 reports of generalised skin reactions, and 3 reports of combined infusion site and skin reactions. There were also reports of anaphylaxis (2 reports) and 8 other adverse events (including headache). In conclusion, Subgam is effective and well tolerated in the treatment of PID.Trial registrationClinicalTrials.gov NCT02247141.

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Plasma pharmacokinetic profile and efficacy of meloxicam administered subcutaneously and intramuscularly to sheep.

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