scholarly journals Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report

2021 ◽  
Vol 8 ◽  
Author(s):  
Joe S. Smith ◽  
Jonathan P. Mochel ◽  
Windy M. Soto-Gonzalez ◽  
Rebecca R. Rahn ◽  
Bryanna N. Fayne ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Half Life ◽  
Plasma Clearance ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Study Objective ◽  
Elimination Half Life ◽  
Elimination Half

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats.Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats.Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis.Results: Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 μg/mL, 0.8 h, and 0.2 hr*μg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study.Conclusion: The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

scholarly journals Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

2020 ◽  
Vol 7 ◽  
Author(s):  
Jeff D. Olivarez ◽  
Amanda J. Kreuder ◽  
Dane M. Tatarniuk ◽  
Larry W. Wulf ◽  
Katarzyna A. Dembek ◽  
...  
Keyword(s):  
Half Life ◽  
Plasma Clearance ◽  
Compartmental Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Tissue Samples ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Edible Tissues ◽  
Neonatal Calves

Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species.Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing.Methods: Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS.Results: Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration.Conclusion: The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.

Effect of the Addition of Ciprofloxacin on Theophylline Pharmacokinetics in Subjects Inhibited by Cimetidine

1992 ◽  
Vol 26 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Robin L. Davis ◽  
Ronald W. Quenzer ◽  
H. William Kelly ◽  
J. Robert Powell
Keyword(s):  
Half Life ◽  
Repeated Measures ◽  
Enzyme Inhibitors ◽  
Enzyme Inhibitor ◽  
Combined Treatment ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Microsomal Enzyme ◽  
Elimination Half Life ◽  
Elimination Half

OBJECTIVE: Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents. The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine. Ciprofloxacin was used as the second inhibitor. DESIGN: In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug-free. SETTING: National Institutes of Health-funded General Clinical Research Center. PARTICIPANTS: Eight normal volunteers (6 men, 2 women; mean age 25.2 y). OUTCOME MEASURES: Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis. Statistical analysis of the data for differences between treatments was assessed by ANOVA for repeated measures. RESEARCH: When administered alone, ciprofloxacin and cimetidine caused a significant increase in theophylline elimination half-life and a decrease in clearance. Theophylline elimination half-life was significantly longer during combined therapy compared with either drug alone. Theophylline clearance was lower during combined treatment, although this relationship did not reach statistical significance. CONCLUSIONS: The addition of a second enzyme inhibitor in subjects receiving maximally inhibiting doses of cimetidine can produce a further decrease in the hepatic metabolism of drugs that are metabolized by the cytochrome P-450 microsomal enzyme system. As cimetidine and ciprofloxacin are frequently used together for a variety of common clinical indications, clinicians should be aware of this drug interaction and should consider that a similar effect may occur when other enzyme inhibitors are used concomitantly.

Epidural, Cerebrospinal Fluid, and Plasma Pharmacokinetics of Epidural Opioids (Part 2)

2003 ◽  
Vol 99 (2) ◽  
pp. 466-475 ◽  
Author(s):  
Christopher M. Bernards ◽  
Danny D. Shen ◽  
Emily S. Sterling ◽  
Jason E. Adkins ◽  
Linda Risler ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Epidural Space ◽  
Drug Concentration ◽  
Half Life ◽  
Sampling Site ◽  
Pharmacokinetic Parameters ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Plasma Pharmacokinetics ◽  
Venous Plasma

Background The ability of epinephrine to improve the efficacy of epidurally administered drugs is assumed to result from local vasoconstriction and a consequent decrease in drug clearance. However, because drug concentration in the epidural space has never been measured, our understanding of the effect of epinephrine on epidural pharmacokinetics is incomplete. This study was designed to characterize the effect of epinephrine on the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids. Methods Morphine plus alfentanil, fentanyl, or sufentanil was administered epidurally with and without epinephrine (1:200,000) to pigs. Opioid concentration was subsequently measured in the epidural space, central venous plasma, and epidural venous plasma, and these data were used to calculate relevant pharmacokinetic parameters. Results The pharmacokinetic effects of epinephrine varied by opioid and by sampling site. For example, in the lumbar epidural space, epinephrine increased the mean residence time of morphine but decreased that of fentanyl and sufentanil. Epinephrine had no effect on the terminal elimination half-life of morphine in the epidural space, but it decreased that of fentanyl and sufentanil. In contrast, in the lumbar intrathecal space, epinephrine had no effect on the pharmacokinetics of alfentanil, fentanyl, or sufentanil, but it increased the area under the concentration-time curve of morphine and decreased its elimination half-life. Conclusions The findings indicate that the effects of epinephrine on the spinal pharmacokinetics of these opioids are complex and often antithetical across compartments and opioids. In addition, the data clearly indicate that the pharmacokinetic effects of epinephrine in spinal "compartments" cannot be predicted from measurements of drug concentration in plasma, as has been assumed for decades.

scholarly journals Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose

2016 ◽  
Vol 73 (2) ◽  
pp. 146-151
Author(s):  
Snezana Djordjevic ◽  
Jasmina Jovic-Stosic ◽  
Vesna Kilibarda ◽  
Zoran Segrt ◽  
Natasa Perkovic-Vukcevic
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Half Life ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Serum Samples ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Limit Of Quantitation

Backgound/Aim. Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylline may reduce the need for repeated dosing of flumazenil in patients with acute diazepam poisoning. The aim of this study was to introduce a reliable and accurate method for determining the concentration of flumazenil after therapeutic application in patients with acute poisoning, and using that method to assess whether the kinetics of flumazenil change in the presence of aminophylline (combination of theophylline and ethylenediamine in a 2 : 1 ratio) applied as concomitant therapy. Methods. Blood samples from patients with acute diazepam poisoning that received flumazenil at the dose of 0.5 mg, or the same dose with 3 mg/kg of body weight of aminophylline, were collected 1, 3, 10, 30, 60, 120 and 240 min after its intravenous administration. Samples were prepared by solid-phase extraction on Oasis HLB cartridges with ethylacetate as extracting agens. Flumazenil was determined by liquid chromatography with mass spectrometry (LC-MS) in single ion monitoring mode at m/z 304. Separation of flumazenil from matrix compound was performed on Lichrospher RP-8 column using the mixture of acidic acetonitrile and 20 mM of ammonium acetate in water (55 : 45) as a mobile phase. Results. The applied analitycal method showed excellent recovery (94.65%). The obtained extracts were much cleaner than the extracts obtained by the same extractant in the process of liquid-liquid extraction. The limit of detection of the LC-MS method described in this paper was 0.5 ng/mL and the limit of quantitation was 1 ng/mL. In the patients treated with both flumazenil and aminophylline, the elimination constant for flumazenil was significantly lower and the elimination half-life was longer (p < 0.05) in comparison with the same parameters in the patients who received flumazenil alone. Conclusion. The applied LC-MS method for the determination of flumazenil in serum samples of patients with acute diazepam poisoning is rapid, sensitive, precise and specific. Concomitant use with theophylline significantly prolonged elimination of flumazenil during the treatment of acute poisonings with diazepam.

scholarly journals Azelastine and suplatast shorten the distribution half-life of IgE in rats

2002 ◽  
Vol 11 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Kazuhiko Hanashiro ◽  
Yoshihiro Tokeshi ◽  
Toshiyuki Nakasone ◽  
Masanori Sunagawa ◽  
Mariko Nakamura ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Rate Constants ◽  
Half Life ◽  
Wistar Rats ◽  
Immunoglobulin E ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Distilled Water ◽  
Elimination Half Life ◽  
Elimination Half

We aim to clarify whether suplatast and azelastine (anti-allergic drugs) can shorten the half-life of immunoglobulin E (IgE) in the circulating blood. Thirty Wistar rats were divided into six groups. Distilled water or anti-allergic drugs were given orally for 6 days after the first sensitization. Two milligrams of monoclonal dinitrophenyl (DNP)-specific rat IgE was administered to the rats, which had been given suplatast or azelastine orally. The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. The elimination half-life of rat IgE was about 12 h irrespective of the sensitized state. The intercompartmental rate constants (KctandKtc) in the suplatast-administered or azelastine-administered group were larger than those of the distilled water-administered group under non-sensitized conditions. These findings suggested that the anti-allergic drugs used in the present study facilitated the excretion of IgE from the circulation in rats.

Clinical and Pharmacokinetic Profiles of Digoxin Immune Fab in Four Patients with Renal Impairment

DICP ◽  
1991 ◽  
Vol 25 (12) ◽  
pp. 1315-1320 ◽  
Author(s):  
Nancy M. Allen ◽  
Gary D. Dunham ◽  
Jeffrey M. Sailstad ◽  
John W.A. Findlay
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Half Life ◽  
Severe Renal Impairment ◽  
Digoxin Concentration ◽  
Pharmacokinetic Data ◽  
Elimination Half Life ◽  
Time Profiles ◽  
Elimination Half ◽  
Total Body

Minimal pharmacokinetic data on digoxin immune Fab are currently available, especially in patients with impaired renal function. The serum concentration-time profiles of total digoxin, free digoxin, and digoxin immune Fab in four patients with moderate to severe renal impairment who received digoxin immune Fab are presented. The calculated elimination half-life of digoxin immune Fab was 25–73 hours. The calculated elimination half-life of total digoxin was 24–72 hours. Free digoxin concentrations rebounded to a peak of 1–2.9 ng/mL 44–97 hours after the administration of digoxin immune Fab. The areas under the curve for digoxin immune Fab were 213–1026 μg·h/mL, and total body clearances were 2.3–7.1 mL/min. The total digoxin concentrations peaked at 14–33 times the pre-Fab digoxin concentrations 5–30 hours after digoxin immune Fab administration. In comparing these data with data available from patients with normal renal function, the half-life of digoxin immune Fab and total digoxin was longer, the peak total digoxin concentration occurred later, the ratio of the peak total digoxin concentration to pre-Fab digoxin concentration was larger, and the rebound in free digoxin occurred later in patients with renal impairment. The Fab dose should not be reduced in patients with renal impairment; however, post-Fab monitoring should be extended to compensate for the prolonged half-life of Fab and later rebound of free digoxin.

Measured Context-sensitive Half-times of Remifentanil and Alfentanil

1995 ◽  
Vol 83 (5) ◽  
pp. 968-975 ◽  
Author(s):  
Atul Kapila ◽  
Peter S. A. Glass ◽  
James R. Jacobs ◽  
Keith T. Muir ◽  
David J. Hermann ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Half Life ◽  
Computer Modelling ◽  
Constant Infusion ◽  
Pharmacokinetic Parameters ◽  
Half Time ◽  
Elimination Half Life ◽  
Context Sensitive ◽  
Elimination Half ◽  
True Time

Abstract Background The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from computer modelling using known pharmacokinetic parameters. The modelled context-sensitive half-time for a 3-h infusion of alfentanil is 50–55 min and is 3 min for remifentanil. The terminal elimination half-life is 111 min for alfentanil and 12–30 min for remifentanil. It has not been tested whether the modelled context-sensitive half-time reflects the true time for a 50% decrease in drug concentration or drug effect.

scholarly journals Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

2013 ◽  
Vol 84 (1) ◽  
Author(s):  
Gabriela A. Albarellos ◽  
Laura Montoya ◽  
Graciela A.A. Denamiel ◽  
Sabrina M. Passini ◽  
María F. Landoni
Keyword(s):  
Plasma Concentration ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Half Life ◽  
Pharmacokinetic Profile ◽  
Maximum Plasma ◽  
Elimination Half Life ◽  
Concentration Time ◽  
Elimination Half ◽  
Intravenous And Oral Administration

The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31) and streptococci (n = 23) strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous) and 16.58 µg/mL ± 0.90 µg/mL (oral). The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous) and 1.84 ± 0.97 (oral). The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively). In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

scholarly journals Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Tatiane Maria de Lima Souza Brioschi ◽  
Simone Grigoleto Schramm ◽  
Eunice Kazue Kano ◽  
Eunice Emiko Mori Koono ◽  
Ting Hui Ching ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Healthy Subjects ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Open Model ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Overnight Fasting ◽  
Tablet Formulations

The purpose of this study was to investigate cyclobenzaprine pharmacokinetics and to evaluate bioequivalence between two different tablet formulations containing the drug. An open, randomized, crossover, single-dose, two-period, and two-sequence design was employed. Tablets were administered to 23 healthy subjects after an overnight fasting and blood samples were collected up to 240 hours after drug administration. Plasma cyclobenzaprine was quantified by means of an LC-MS/MS method. Pharmacokinetic parameters related to absorption, distribution, and elimination were calculated. Cyclobenzaprine plasma profiles for the reference and test products were similar, as well as absorption pharmacokinetic parameters AUC (reference: 199.4 ng∗h/mL; test: 201.6 ng∗h/mL), (reference: 7.0 ng/mL; test: 7.2 ng/mL), and (reference: 4.5 h; test: 4.6 h). Bioequivalence was evaluated by means of 90% confidence intervals for the ratio of AUC (93%–111%) and (93%–112%) values for test and reference products, which were within the 80%–125% interval proposed by FDA. Cyclobenzaprine pharmacokinetics can be described by a multicompartment open model with an average rapid elimination half-life () of 3.1 hours and an average terminal elimination half-life () of 31.9 hours.

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