Home About us Contact
|
Home About us Contact | ||
|
|
||
Short Elimination Half-life (short + elimination_half-life)
Selected AbstractsNew insights into the biotransformation and pharmacokinetics of oxaliplatinJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2009Elin Jerremalm Abstract Oxaliplatin is used primarily in the treatment of metastatic colorectal cancer. In this minireview, we discuss potentially important biotransformation pathways in light of its short elimination half-life in vivo. We also highlight new information achieved using a selective analytical technique to measure intact oxaliplatin in pharmacokinetic studies (comprising intravenous, intraperitoneal, and intrahepatic administration) and compare to results obtained by measurements of total platinum. The use of selective analytical techniques is strongly recommended giving kinetic parameters of the parent compound and not only to a complex mixture of platinum containing endogenous compounds. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3879,3885, 2009 [source] Efficacy and Pharmacokinetics of Pantoprazole in AlpacasJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2010G.W. Smith Background: Despite frequent clinical use, information about the pharmacokinetics and efficacy of pantoprazole in camelids is not available. Objectives: To examine the pharmacokinetics of both IV and SC pantoprazole and to determine whether pantoprazole administration would increase 3rd compartment pH in alpacas. Animals: Six healthy adult alpacas. Methods: Alpacas were fitted with a 3rd compartment cannula for measuring gastric pH. After recovery, alpacas received 1 mg/kg pantoprazole IV, q24h for 3 days or 2 mg/kg SC q24h for 3 days. Alpacas received both IV and SC pantoprazole, with a minimum of 3 weeks between treatments. Third compartment pH was recorded and plasma samples were taken for pharmacokinetic analysis. Results: Pantoprazole induced a slow but sustained increase in 3rd compartment pH when given by both the IV and SC routes. Third compartment pH was significantly increased as compared with baseline values (1.81 ± 0.7; mean ± SD) at 24 (2.47 ± 0.8), 48 (3.53 ± 1.0) and 72 hours (4.03 ± 1.3) after daily IV administration of pantoprazole. Third compartment pH increased from 1.73 ± 0.6 at baseline to 3.05 ± 1.1, 4.02 ± 1.4, and 3.61 ± 1.6 at 24, 48, and 72 hours after SC administration, respectively. Pharmacokinetic analysis demonstrated that pantoprazole had a short elimination half-life (0.47 + 0.06 h) and a high clearance rate (12.2 ± 2.9 mL/kg/min) after both IV and SC administration. Conclusions and Clinical Relevance: Based on the results of this study, pantoprazole represents a safe and effective drug for increasing 3rd compartment pH in camelids. Either IV or SC administration is likely to be an effective treatment for gastric ulcers. [source] Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horsesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009R. L. LINARDI Methadone hydrochloride is a synthetic ,-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (Vd/F) and short elimination half-life (t1/2). The mean of the estimated t1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated Cmax (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively. [source] Evaluation of pharmacokinetics, brain levels and protein binding of centpropazine in ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2004Venkatesh Atul Bhattaram Abstract The pharmacokinetics of centpropazine (CNPZ), an antidepressant, was studied in rats. CNPZ was administered to groups of rats (n=3 to 5) via oral (40 mg/kg), intravenous (5 mg/kg), intraperitoneal (5 mg/kg) and intraduodenal (4 and 8 mg/kg) routes. The AUCs of CNPZ were estimated and the bioavailabilities were calculated. CNPZ was characterized by a short elimination half-life (39.5 min), a high clearance (118 ml/min/kg) and a relatively large volume of distribution (1945 ml/kg) after intravenous administration. After oral administration CNPZ exhibited a very low oral bioavailability (,0.2%). The total first pass effect (Egit+liver) was calculated as 98.7%. The bioavailability of CNPZ was similar when administered by intraduodenal and oral routes. CNPZ readily penetrated into the brain and reached Cmax by 30 min post oral dosing. About 92.0%±0.8% of the drug was bound to serum proteins. Low oral bioavailability of CNPZ following oral administration is likely due to its metabolism by intestinal mucosa and liver. Copyright © 2004 John Wiley & Sons, Ltd. [source] Pharmacokinetics and metabolism of the novel synthetic C -nucleoside, 1-(2-deoxy- , -D-ribofuranosyl)-2,4-difluoro- 5-iodobenzene: a potential mimic of 5-iodo-2,-deoxyuridineBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2002Panteha Khalili Abstract 1-(2-Deoxy- , -D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (5-IDFPdR) is one of the several unnatural 1-(2-deoxy- , -D-ribofuranosyl)-2,4-difluoro-5-substituted-benzenes recently synthesized for evaluation as anticancer, antiviral and diagnostic imaging agents. This class of C -nucleosides was designed to exploit several potential advantages relative to classical 5-substituted-2,-deoxyuridines, including stability towards phosphorolysis by pyrimidine phosphorylase, increased lipophilicity that may alter their ability to cross the blood,brain-barrier, and a greater resistance towards catabolism and deiodination. The physiochemical evaluation of 5-IDFPdR showed high lipophilicity (log P=2.8), moderately high protein binding (70,75%), stability towards phosphorolysis (e.g. no evidence of metabolic deglycosylation) by thymidine phosphorylase, and minimal microsomal metabolism in vitro. Pharmacokinetic studies of 5-IDFPdR in rat were characterized by a short elimination half-life (9,12 min), modest urinary elimination in pooled 0,24 h urine specimens (10,14%, including 2% as unconjugated drug) and high oral bioavailability (F=0.96). Both glucuronide and sulfate metabolites were present in urine. Glucuronidation was the predominant conjugation pathway. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||