Effects of housing environment on oral absorption of acetaminophen in healthy Beagles

2022 ◽  
pp. 1-6
Author(s):  
Melanie Madsen ◽  
Hiroko Enomoto ◽  
Kristen Messenger ◽  
Mark G. Papich
Keyword(s):  
High Pressure ◽  
Liquid Chromatography ◽  
Oral Absorption ◽  
Compartment Model ◽  
Lag Time ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Housing Environment ◽  
Normal Environment ◽  
Best Fit

Abstract OBJECTIVE To evaluate the effects of housing environment on oral absorption of acetaminophen in dogs. ANIMALS 6 healthy Beagles. PROCEDURES Acetaminophen (325 mg, PO; mean dose, 31.1 mg/kg) was administered in a crossover study design with dogs housed in their normal environment or in a cage in an unfamiliar environment. There was a 7-day washout period between phases. Blood samples were collected for 24 hours following acetaminophen administration, and plasma acetaminophen concentrations were determined with high-pressure liquid chromatography. RESULTS A 2-compartment model with lag time was the best fit for both phases of the study. None of the primary or secondary pharmacokinetic parameters were significantly different between the 2 housing environments. CLINICAL RELEVANCE Findings suggested that in dogs, housing environment (normal environment vs a cage in an unfamiliar environment) did not significantly affect oral absorption and, by extension, gastric emptying of acetaminophen.

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

2015 ◽  
Vol 18 (2) ◽  
pp. 371-377 ◽  
Author(s):  
R. Sokół ◽  
M. Raś-Noryńska ◽  
M. Michalczyk ◽  
A. Jasiecka ◽  
H. Ziółkowski ◽  
...  
Keyword(s):  
High Pressure ◽  
Liquid Chromatography ◽  
Blood Plasma ◽  
Drug Administration ◽  
High Pressure Liquid Chromatography ◽  
Drug Absorption ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Fecal Samples ◽  
Single Bolus

Abstract The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug’s pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (tmax: 21.89±11.43 h) in autumn than in spring (tmax: 9.78±8.97 h). Maximum concentrations (Cmax) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment. The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.

scholarly journals Pharmacokinetic and bioavailability study of lercanidipine hydrochloride fast disintegrating tablets in rabbits by high-performance liquid chromatography

2020 ◽  
Vol 11 (4) ◽  
pp. 7289-7292
Author(s):  
Seema Saini ◽  
Rajeev Garg
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Plasma Concentration ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Blood Samples ◽  
Fast Disintegrating Tablet ◽  
Fast Disintegrating Tablets ◽  
Lercanidipine Hydrochloride

In the present study, fast disintegrating tablets of Lercanidipine Hydrochloride (LFDT) were tested in vivo in the buccal cavity of the rabbits. Various pharmacokinetic parameters were analysed in the study, including maximum measured plasma concentration (Cmax), time of maximum measured plasma concentration (tmax) and area under the plasma concentration vs time curve (AUC). Also, the comparative study of the Lercanidipine Hydrochloride fast disintegrating tablets (LFDT) was performed with the marketed conventional tablets of the drug (LMKT). The technique selected for the bioanalytical analysis of the blood samples of the rabbits for pharmacokinetic data computation was High-Performance Liquid Chromatography. An already well-established and validated method was used to analyse the blood samples of the rabbits. The results revealed that the rate of absorption was improved for fast disintegrating tablets of Lercanidipine Hydrochloride (LFDT) as compared to the marketed conventional tablets of the drug (LMKT). This indicated that drug was rapidly absorbed from the fast disintegrating tablet and attained elevated plasma concentration in a short interval after dosing than the marketed formulation. However, the value of tmax was drastically shorter for LFDT than the LMKT. The average peak plasma concentration also designated a rise in the extent of absorption (AUC). From the present study, it was concluded that the fast disintegrating tablet batch (LFDT) had much more improved pharmacokinetic parameters as compared to its conventional marketed counterpart (LMKT).

Hormonal responses associated with early hyperglycemia after graded hemorrhage in dogs

1986 ◽  
Vol 251 (5) ◽  
pp. E597-E603
Author(s):  
M. K. McLeod ◽  
D. E. Carlson ◽  
D. S. Gann
Keyword(s):  
High Pressure ◽  
Nitrous Oxide ◽  
Liquid Chromatography ◽  
Portal Vein ◽  
Femoral Artery ◽  
Femoral Vein ◽  
Immunoreactive Insulin ◽  
Flow Measurements ◽  
Hormonal Responses ◽  
Blood Samples

Trained, awake, splenectomized dogs (n = 17) were studied to examine potential mechanisms for early hyperglycemia after hemorrhage (H). Animals were surgically prepared under halothane-nitrous oxide 3 days before the experiment. Chronic catheters were placed aseptically in the portal vein (PV), femoral vein, and femoral artery. Electromagnetic flow probes were placed around the PV and hepatic artery. After an overnight fast, dogs were hemorrhaged 10, 20, or 30% of their estimated blood volume in 3 min. Flow measurements and blood samples for glucose (G), immunoreactive insulin (IRI), immunoreactive glucagon (IRG), catecholamines (C), and cortisol (F) were taken prior to H and from 5 min to 8 h post-H. Plasma IRI, IRG, and F were measured by radioimmunoassay, plasma C by high-pressure liquid chromatography, and G by a glucose oxidase method. Peripheral G did not change after 10% H but increased significantly after 20 and 30% H from 10 min to 2 h. Similarly, peripheral C did not change after 10% H but increased significantly from 10 min to 2 h after 20 and 30% H. In contrast, the portal venous delivery of IRG did not increase significantly until at least 1 h after any magnitude of H. Peripheral IRI did not change after any magnitude of H. However, portal venous delivery of IRI decreased significantly from 20 min to 6 h after 10% H. Plasma F increased significantly in peripheral blood after all magnitudes of H. These results indicate that an increase in the release of IRG occurs too late to account for the early hyperglycemia that occurs during the 1st h following H.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of Nonsteroidal Anti-inflammatory Drugs to Deaths Associated With Peptic Ulcer Disease

2001 ◽  
Vol 125 (12) ◽  
pp. 1572-1574 ◽  
Author(s):  
Michael Tsokos ◽  
Achim Schmoldt
Keyword(s):  
High Pressure ◽  
Peptic Ulcer ◽  
Liquid Chromatography ◽  
Sudden Death ◽  
Peptic Ulcer Disease ◽  
High Pressure Liquid Chromatography ◽  
Temporal Association ◽  
Blood Samples ◽  
Ulcer Disease ◽  
Inflammatory Drugs

Abstract Context.—Of the side effects occurring in temporal association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), peptic ulcer disease is reported most often. Objectives.—To (1) provide information on the temporal association between fatal peptic ulcer presenting as sudden death and NSAID use prior to death, and (2) to examine the diagnostic efficiency of postmortem determination of NSAID levels using high-pressure liquid chromatography. Design.—Prospective autopsy study of all cases of sudden death associated with peptic ulcer disease from a total of 1139 medicolegal autopsies performed during a 12-month period. Methods.—Postmortem femoral blood samples were analyzed for NSAIDs using high-pressure liquid chromatography, and specimens of gastric and duodenal mucosa were examined for coexisting pathologic conditions. Results.—Twelve fatalities that occurred out of hospital as a result of peptic ulcer disease and presented as sudden death were identified. Autopsy blood samples were positive for NSAIDs in 7 cases (ibuprofen in 4 cases, levels 0.8 to 1.4 μg/mL; diclofenac in 2 cases, levels 0.6 and 1.6 μg/mL; and ketoprofen in 1 case, level 0.3 μg/mL). The ages of the affected individuals (3 men, 4 women) ranged from 43 to 60 years. No other drugs, including corticosteroids, anticoagulants, salicylic acid, and salicylates, were present. Microscopic examination revealed no pathologic antemortem mucosal conditions in any of the cases. Conclusions.—For the postmortem elucidation of etiopathogenetic factors contributing to fatal peptic ulcer disease, high-pressure liquid chromatography to determine NSAID levels in autopsy blood samples is of considerable diagnostic benefit, especially when combined with histology. The number of cases of sudden death involving younger individuals dying as a result of peptic ulcer disease in temporal association with preceding use of NSAIDs seems to be underestimated from the clinical viewpoint due to the underrepresentation of out-of-hospital fatalities in the field of clinical pathology.

Ginger Significantly Decreased the Oral Bioavailability of Cyclosporine in Rats

2006 ◽  
Vol 34 (05) ◽  
pp. 845-855 ◽  
Author(s):  
Hsiu-Mei Chiang ◽  
Pei-Dawn Lee Chao ◽  
Su-Lan Hsiu ◽  
Kuo-Ching Wen ◽  
Shang-Yuan Tsai ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Therapeutic Index ◽  
Zingiber Officinale ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Fluorescence Polarization Immunoassay ◽  
Crossover Designs ◽  
Narrow Therapeutic Index ◽  
Blood Samples ◽  
Zingiber Officinale Roscoe

Ginger (roots of Zingiber officinale ROSCOE) is a popular spice and herbal medicine worldwide. Cyclosporine is clinically used as an important immunosupressant with narrow therapeutic index. This study attempted to investigate the effect of ginger juice on the pharmacokinetics of cyclosporine in rats. Rats were orally administered cyclosporine alone and in combination with ginger juice (5 ml/kg) concomitantly, as well as 2 hours after the ginger juice, respectively, in crossover designs. In addition, rats were intravenously administered cyclosporine with and without an oral dose of ginger juice (5 ml/kg). The blood samples were withdrawn via cardiopuncture at determined time points and cyclosporine concentrations were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters of cyclosporine were calculated using a non-compartment model of WINNONLIN. The results indicated that concomitant intake of ginger significantly decreased Cmaxand AUC0–tof oral cyclosporine by 70.9% and 63.1%, respectively. The intake of ginger 2 hours before cyclosporine significantly decreased Cmaxand AUC0–tby 51.4% and 40.3%, respectively. In contrast, the pharmacokinetics of intravenous cyclosporine not altered by orally in combination with ginger juice. In conclusion, ginger significantly decreased the oral bioavailability of cyclosporine, and the interaction should occur at the absorption phase. Patients treated with cyclosporine should be discouraged from using ginger products to ensure the efficacy of cyclosporine.

Propofol Alters the Pharmacokinetics of Alfentanil in Healthy Male Volunteers

2001 ◽  
Vol 94 (6) ◽  
pp. 949-957 ◽  
Author(s):  
Martijn J. Mertens ◽  
Jaap Vuyk ◽  
Erik Olofsen ◽  
James G. Bovill ◽  
Anton G. L. Burm
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Venous Blood ◽  
Compartment Model ◽  
Lag Time ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Male Volunteers ◽  
Elimination Clearance ◽  
End Tidal

Background The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil. Methods The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2 min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 microg/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed. Results A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model. Conclusions Propofol alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of alfentanil.

scholarly journals Influence of Alpha-1 Glycoprotein Acid Concentrations and Variants on Atazanavir Pharmacokinetics in HIV-Infected Patients Included in the ANRS 107 Trial

2009 ◽  
Vol 54 (2) ◽  
pp. 614-619 ◽  
Author(s):  
A. Barrail-Tran ◽  
F. Mentré ◽  
C. Cosson ◽  
C. Piketty ◽  
C. Chazallon ◽  
...  
Keyword(s):  
Protein Binding ◽  
Compartment Model ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Binding Characteristics ◽  
Clinical Consequences

ABSTRACT Atazanavir is an HIV-1 protease inhibitor with high protein binding in human plasma. The objectives were first to determine the in vitro binding characteristics of atazanavir and second to evaluate whether plasma protein binding to albumin and alpha-1 glycoprotein acid (AAG) influences the pharmacokinetics of atazanavir in HIV-infected patients. For the in vitro study, atazanavir protein binding characteristics were determined in AAG- and albumin-containing purified solutions. Atazanavir was found to bind AAG on a high-affinity saturable site (association constant, 4.61 × 105 liters/mol) and albumin on a low-affinity nonsaturable site. For the in vivo study, blood samples from 51 patients included in trial ANRS 107—Puzzle 2 were drawn prior to drug intake at week 6. For 10 patients included in the pharmacokinetic substudy, five additional blood samples were collected during one dosing interval at week 6. Atazanavir concentrations were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Albumin concentrations, AAG concentrations, and phenotypes were also measured in these patients. Concentrations of atazanavir were modeled using a population approach. A one-compartment model with first-order absorption and elimination best described atazanavir pharmacokinetics. Atazanavir pharmacokinetic parameters and their interindividual variabilities were as follows: absorption rate constant (ka ), 0.73 h−1 (139.3%); apparent clearance (CL/F), 13.3 liters/h (26.7%); and apparent volume of distribution (V/F), 79.7 liters (27.0%). Atazanavir CL/F decreased significantly when alanine aminotransferase and/or AAG levels increased (P < 0.01). The ORM1*S phenotype also significantly increased atazanavir V/F (P < 0.05). These in vivo results indicate that atazanavir pharmacokinetics is moderately influenced by its protein binding, especially to AAG, without expected clinical consequences.

scholarly journals Clinical pharmacokinetics in optimal gentamicin dosing regimen in neonates

Open Medicine ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. 485-490
Author(s):  
Katarina Vučićević ◽  
Zorica Rakonjac ◽  
Borisav Janković ◽  
Sandra Vezmar Kovačević ◽  
Branislava Miljković ◽  
...  
Keyword(s):  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Variability ◽  
Dosing Regimen ◽  
Clinical Pharmacokinetics ◽  
Blood Samples ◽  
Dosing Interval ◽  
Daily Dose ◽  
Trough Levels

AbstractGentamicin is readily used for suspected or proven sepsis in neonates, yet it shows considerable inter-individual pharmacokinetic variability, which limits achievements of therapeutic levels. Hence, the aim of this study was to compare peak and trough gentamicin concentrations according to dosing regimen, to evaluate pharmacokinetic parameters, and to consider adjustments of dosing regimen. Babies with infection were treated with 1 h infusion, and daily dose of 5 or 7.5 mg/kg depending on the age. Patients were randomized into two groups: I — dosing interval 12 h (n=8), II — 24 h (n=11). Two steady-state blood samples were obtained. Pharmacokinetic parameters were calculated using one-compartment model. The results showed a difference (p<0.05) in peak gentamicin concentrations between the groups, and tendency of lower trough levels in the group II. Calculated pharmacokinetic parameters included the volume of distribution (Vd) 0.52±0.47 l/kg, clearance (CL) 0.055±0.036 l/hkg and a half-life (t1/2) of 6.89±3.21 h. Based on the method for dosing regimen adjustments, there was a need to extend dosing interval to 36 h in 6 patients

Sign in / Sign up

Export Citation Format

Share Document