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- Gabrielsson, Johan, et al.
(author)
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Maxsim2-Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics.
- 2014
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In: Computer methods and programs in biomedicine. - : Elsevier BV. - 1872-7565 .- 0169-2607. ; 113, s. 815-829
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Journal article (peer-reviewed)abstract
- We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration-time and/or response-time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration-response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.
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- Ingvast Larsson, Carina, et al.
(author)
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Clinical pharmacology of methadone in dogs
- 2010
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In: Veterinary Anaesthesia and Analgesia. - : Elsevier BV. - 1467-2987 .- 1467-2995. ; 37:1, s. 48-56
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Journal article (peer-reviewed)abstract
- Objective: To investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs. Study design Randomized, cross-over, experimental trial. Animals Nine adult dogs (beagle and beagle cross breeds), four males and five females. Methods Methadone hydrochloride, 0.4 mg kg-1, was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol. Results After IV administration, the plasma concentration of methadone at 10 minutes was 82.1 +/- 9.2 ng mL-1 (mean +/- SD), the terminal half-life was 3.9 +/- 1.0 hours, the volume of distribution 9.2 +/- 3.3 L kg-1 and plasma clearance 27.9 +/- 7.6 mL minute-1 kg-1. After SC administration, time to maximal plasma concentration was 1.26 +/- 1.04 hours and maximal plasma concentration of methadone was 23.9 +/- 14.4 ng mL-1, the terminal half-life was 10.7 +/- 4.3 hours and bioavailability was 79 +/- 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic. Conclusion and clinical relevance When methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.
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- Ingvast Larsson, Carina, et al.
(author)
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Pharmacokinetics of meloxicam in adult goats and its analgesic effect in disbudded kids
- 2011
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In: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 34:1, s. 64-69
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Journal article (peer-reviewed)abstract
- The pharmacokinetics and analgesic effect of the nonsteroidal anti-inflammatory drug meloxicam (0.5 mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n = 8) after single intravenous and oral administration. The analgesic effect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n = 6) once daily and their siblings (n = 5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9 ± 1.7 h, steady-state volume of distribution was 0.245 ± 0.06 L/kg, and total body clearance was 17.9 ± 4.3 mL/h/kg. After oral administration bioavailability was 79 ± 19%, C(max) was 736 ± 184 ng/mL, T(max) was 15 ±5 h, although the terminal half-life was similar to the intravenous value, 11.8 ± 1.7 h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups.
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- Olsén, Lena, et al.
(author)
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Intramuscular administration of sodium benzylpenicillin in horses as an alternative to procaine benzylpenicillin
- 2013
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In: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 95:1, s. 212-218
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Journal article (peer-reviewed)abstract
- The aim was to supply information about the possibility of replacing the procaine salt with the sodium salt for benzylpenicillin IM treatment in horse in order to diminish the risk for procaine adverse effects. In a crossover study eight horses were given 15 mg/kg sodium benzylpenicillin (Na-pc) twice daily or procaine benzylpenicillin (control) once daily IM for four days. The half-life of Na-pc was 1.9 h, peak concentration was 14,600 ng/mL reached after about 23 min. Trough plasma concentration Was 281 ng/mL and protein binding 62.8%. The fT > MIC for Staphylococcus aureus was 63% and 100% for Streptococcus equi subsp. equi and Streptococcus zooepidemicus, indicating an adequate antimicrobial therapy. However, Na-pc cannot be recommended from a welfare point of view since the horses showed more pain related behaviour and more pain and swelling compared to the control treatment.
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- Olsén, Lena, et al.
(author)
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Methadone in healthy goats : Pharmacokinetics, behaviour and blood pressure
- 2013
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In: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 95:1, s. 231-237
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Journal article (peer-reviewed)abstract
- The pharmacokinetics and effects of the opioid methadone on behaviour, arterial blood pressure, heart rate and haematocrit were studied in goats. Two goats received methadone (0.2 mg/kg) intravenously and the terminal half-life was 88 and 91 min, the volume of distribution 8.4 and 6.1 L/kg, and clearance 86 and 123 mL/min/kg. In a crossover study eight goats received methadone (0.6 mg/kg) or 0.15 M NaCl subcutaneously (SC). After SC administration bioavailability was complete and the terminal half-life was 215 +/- 84 min (mean +/- SD), T-max 31 +/- 15 min and C-max 45 +/- 11 ng/mL. Blood pressure and haematocrit increased while heart rate did not change. The goats did not ruminate and they climbed, scratched, gnawed and showed tail-flicking after SC methadone in contrast to NaCl administration. The use of methadone in goats may be restricted due to the inhibition of rumination and the rather short half-life.
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- Olsén, Lena, et al.
(author)
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Pharmacokinetics and effects of cetirizine in horses with insect bite hypersensitivity
- 2011
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In: The Veterinary Journal. - : Elsevier BV. - 1090-0233 .- 1532-2971. ; 187:3, s. 347-351
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Journal article (peer-reviewed)abstract
- Horses with insect bite hypersensitivity (IBH) have difficulty in completely avoiding allergens, so effective treatment options are required. A randomised, placebo controlled and double blinded field study was conducted to determine the pharmacokinetics and efficacy in reducing dermatitis of the antihistamine cetirizine given orally at 0.4mg/kg twice daily for 3weeks. The influence of protection blankets and stabling were also investigated. The estimated maximum plasma concentration (C(max)) and trough plasma concentration of cetirizine were 135ng/mL and 18ng/mL, respectively. There was no difference in dermatitis reduction between the treatment and placebo groups (P=0.77). The findings indicated that cetirizine was of no apparent benefit in treating IBH at the dose rate tested. The use of blankets and stabling were shown to have favourable influence on the dermatitis (P<0.05) and may be the preferred options to prevent this condition.
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