Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats
ABSTRACT To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats.
7 healthy neutered male client-owned cats.
Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration.
2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 +/- 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 +/- 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 +/- 142 ng/mL and 62.4 +/- 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration.
Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.
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- "P < 0.001. 2004; Bennett et al., 2005; Helms, 2007; MacGregor et al., 2008; Hill et al., 2011, 2014; Miller et al., 2014 "
ABSTRACT: The use of transdermal medications in cats has become popular in veterinary medicine due to the ease of administration compared to oral medication. However, the research to support systemic absorption of drugs applied to the pinna after transdermal administration in cats is limited. The aim of this study was to characterize the percutaneous absorption pharmacokinetics of methimazole in a lipophilic vehicle compared to methimazole in Pluronic(®) lecithin organogel (PLO) using a finite dose applied to feline ear skin in an in vitro Franz cell model. The two formulations of methimazole (10 mg) were applied to the inner stratum corneum of six pairs of feline ears. The receptor medium was sampled up to 30 h post-administration, and methimazole concentrations were measured using high-performance liquid chromatography (HPLC). Histological examination of all ears was undertaken as small differences in the thickness of ear skin may have contributed to inter-individual differences in methimazole absorption between six cats. Methimazole was absorbed more completely across the pinnal skin when administered in the lipophilic vehicle compared to administration in the PLO gel (P < 0.001). © 2015 John Wiley & Sons Ltd.Journal of Veterinary Pharmacology and Therapeutics 02/2015; DOI:10.1111/jvp.12213 · 1.32 Impact Factor
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ABSTRACT: Forced convection boiling in microchannels is studied experimentally under uniform heat flux boundary condition. Several microchannel heat sinks, ranging in height between 5 and 20 μm, have been fabricated using standard micromachining techniques with nucleation sites varying in size etched at the channels bottom surface. The heat flux was provided by a heater integrated at the device back side, while constant water flow rate was supplied by a syringe pump. Boiling curves of device temperature as a function of the input power have been measured for a variety of conditions. The points corresponding to the onset of nucleate boiling and critical heat flux (CHF) are clearly distinguishable. Furthermore, the boiling curves for increasing and decreasing heat flux exhibit a hysteresis loop. The activity of the nucleation sites is found to depend on the channel height. The critical size, above which nucleation sites are active, increases exponentially with the microchannel height, asymptotically approaching a theoretical value.Micro Electro Mechanical Systems, 2004. 17th IEEE International Conference on. (MEMS); 02/2004
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ABSTRACT: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method for the measurement of the novel heart rate-lowering drug ivabradine and its major metabolite, S-18982, was cross-validated in the plasma of eight healthy cats. Plasma concentrations were then determined after single and repeated oral administration of ivabradine. Individual plasma concentrations versus time from each cat were used in compartmental analysis using the commercially available software WinNonlin. Both ivabradine and S-18982 reached their maximum concentrations of 103.33 and 3.86 ng/mL within 1 h. Following repeated administration, areas under the plasma concentration-time curves for ivabradine and S-18982 did not significantly increase. Two-compartmental and one-compartmental models with first-order input and elimination provided the best fit to the data for ivabradine and S-18982, respectively. Both models were combined to produce a single 4-compartment model characterizing ivabradine and S-18982 pharmacokinetics. The results of this study indicate that repeated oral doses of ivabradine produced plasma drug concentrations suitable for 12-h dosing intervals in healthy cats. Furthermore, the analytical assay and combined ivabradine/S-18982 model provide tools for further evaluation of ivabradine pharmacokinetics and pharmacodynamics in future studies in cats.Journal of Veterinary Pharmacology and Therapeutics 12/2010; 34(5):469-75. DOI:10.1111/j.1365-2885.2010.01253.x · 1.32 Impact Factor