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Long Elimination Half-life (long + elimination_half-life)
Selected AbstractsThe novel N -substituted benztropine analog GA2-50 possesses pharmacokinetic and pharmacodynamic profiles favorable for a candidate substitute medication for cocaine abuseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2008Ahmed A. Othman Abstract GA2-50 is a novel N -substituted benztropine analog with improved potency and selectivity for the dopamine transporter. The pharmacokinetic and pharmacodynamic properties of GA2-50 were characterized as a part of its preclinical evaluation as a substitute medication for cocaine abuse. In vitro transport and metabolism studies as well as pharmacokinetic studies in rats were conducted. Effect of GA2-50 on the extracelluar nucleus accumbens (NAc) dopamine levels and on cocaine's induced dopamine elevation was evaluated using intracerebral microdialysis. GA2-50 showed high transcellular permeability despite being a P-glycoprotein substrate. GA2-50 was a substrate of human CYP2D6, CYP2C19, CYP2E1, rat CYP2C11, CYP2D1, CYP3A1, and CYP1A2; with low intrinsic clearance values. In vivo, GA2-50 showed high brain uptake (Ri,,,10), large volume of distribution (Vss,=,37 L/kg), and long elimination half-life (t½,=,19 h). GA2-50 resulted in 1.6- and 2.7-fold dopamine elevation at the 5 and 10 mg/kg i.v. doses. Dopamine elevation induced by GA2-50 was significantly reduced, slower and longer lasting than previously observed for cocaine. GA2-50 had no significant effect on cocaine's induced dopamine elevation upon simultaneous administration. Results from the present study indicate that GA2-50 possesses several attributes sought after for a substitute medication for cocaine abuse. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Selected pharmacokinetic parameters for Cefovecin in hens and green iguanasJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2009L. R. THUESEN The third generation cephalosporin cefovecin has been shown to have an exceptionally long elimination half-life in dogs and cats, making it suitable for antibacterial treatment with a 14-day dosing interval in these species. Pharmacokinetic parameters for cefovecin were investigated in juvenile hens and green iguanas, following subcutaneous injections with 10 mg cefovecin/kg bodyweight. Preliminary studies in eight additional species of birds and reptiles were performed and results were compared with the parameters found in hens and green iguanas. The kinetics were characterized by rapid absorption with peak plasma concentration of 6 ± 2 ,g/mL in hens and 35 ± 12 ,g/mL in green iguanas. The mean plasma half-life for cefovecin was 0.9 ± 0.3 h for hens and 3.9 h in green iguanas. Volume of distribution was 1.6 ± 0.5 L/kg for hens and 0.3 L/kg for green iguanas and clearance was 1252 ± 185 mL·h/kg for hens and 53 mL·h/kg for green iguanas. Results from preliminary studies did not differ notably from those seen in hens and green iguanas. Cefovecin is not suitable for the treatment of bacterial infections with a 14-day dosing interval in hens or green iguanas and seems not to be in a number of other bird and retile species either. [source] The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy catsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000Parton The pharmacokinetics of carprofen, a propionic acid-derived nonsteroidal anti-inflammatory (NSAID), and its effect on gastrointestinal mucosa, complete blood counts (CBC) and biochemical indicators of liver and renal function were investigated in healthy cats using a randomized crossover design. A single dose of 4 mg/kg of carprofen (Zenecarp® Injection), normal saline, or 20 mg/kg of DL-lysine acetyl salicylate (Vetalgine®) was given intravenously (i.v.) to each of five cats with a washout period of 2 weeks between treatments. Endoscopy of the stomach and duodenum 8 h postinjection revealed one acetyl salicylate-(aspirin)-treated cat with minor pinpoint erosions. None of the other cats in the three treatment groups had evidence of bleeding or ulceration. Serum biochemistry measurements of blood urea nitrogen (BUN), alanine transferase (ALT) and alkaline phosphatase (ALP) and complete blood counts (CBC) were not significantly altered from pretreatment values by the single dose of salicylate or carprofen (P < 0.05). Early and extended sample time points suggest that the pharmacokinetics of carprofen in the cat fit a 2-compartment model, with a long elimination half-life (t1/2) of 20.1 ± 16.6 h, an area under the plasma concentration,time curve (AUC) of 637 (± 237) ,g.mL/h and a volume of distribution (Vdss) of 0.14 ± 0.05 L/kg. Intravenously administered aspirin fit a 2-compartment model and had a long elimination half-life (t1/2) of 22.2 ± 3.1 h, an AUC of 3824.2 ± 506.7 ,g.mL/h and a volume of distribution (Vdss) of 0.17 ± 0.01 L/kg. [source] Pharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2001Raquel F. Reinoso Abstract The pharmacokinetics of E-6087, a newly developed cyclooxygenase-2 inhibitor, was studied in rats and dogs after single oral and intravenous doses. In both animal species, E-6087 was characterized by a long elimination half-life (20,35 h), a low plasma clearance (0.10,0.22 l h,1 kg,1) and a relatively large volume of distribution (2,6 l kg,1). Oral bioavailability was lower in dogs than in rats whereas a faster elimination was found in rats. Multiple peaks were present regardless of administration route and animal species, suggesting the existence of enterohepatic circulation. Gender effect on the pharmacokinetics of E-6087 was only found in rats, with greater exposure and longer elimination in females than in males. Food intake reduced the bioavailability (,22%) with no apparent changes in the absorption rate. After oral dosing of 1, 5 and 25 mg kg,1 to rats, linearity was lost at the highest dose due to the low aqueous solubility of E-6087. Drug absorption was improved by micronization. E-6087 and E-6132, (a pharmacologically active metabolite), showed different pharmacokinetics. The higher percentage of E-6087 at early times suggests that E-6087 is the main compound responsible for in vivo activity, although E-6132 would contribute to the activity at later times. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||