Oral Bioavailability of Nizatidine and Ranitidine Concurrently Administered with Antacid

1989 ◽  
Vol 17 (1) ◽  
pp. 62-67 ◽  
Author(s):  
J. P. Desager ◽  
C. Harvengt
Keyword(s):  
High Performance ◽  
Drug Application ◽  
Open Label ◽  
Time Curve ◽  
Open Label Study ◽  
Concentration Time ◽  
Neutralizing Capacity ◽  
Significant Difference ◽  
Student’S T ◽  
Student’S T Test

This four-way crossover open-label study on eight healthy subjects was designed to investigate the effect on bioavailability of orally administered nizatidine given concurrently with an antacid (magnesium hydroxide–aluminium hydroxide mixture). Ranitidine was used as a comparison. Subjects were hospitalized overnight for each drug application which was given as a single dose [nizatidine or ranitidine (300 mg) or antacid (20 ml) of a neutralizing capacity of 50 mmol hydrochloric acid]. Plasma nizatidine or ranitidine concentrations were measured by high performance liquid chromatography. No statistically significant difference occurred in the kinetic profile of nizatidine after antacid administration although it took longer to reach maximum concentration in plasma. The area under the concentration–time curve was also reduced (by ≤10%) and there was a longer lag between administration and absorption. Bioequivalence (Westlake test) for ranitidine in the presence or absence of antacid was confirmed (difference ≤12%). For nizatidine, with or without antacid, the value of the Westlake test was just above the limit for bioequivalence (21.4%), whereas the Student's t-test for related means (one-tailed distribution) gave P = 0.045. There was no clinically relevant nizatidine–antacid interaction at the doses used in this study.

scholarly journals Fosamprenavir plus Ritonavir Increases Plasma Ketoconazole and Ritonavir Exposure, while Amprenavir Exposure Remains Unchanged

2007 ◽  
Vol 51 (8) ◽  
pp. 2982-2984 ◽  
Author(s):  
Mary B. Wire ◽  
Charles H. Ballow ◽  
Julie Borland ◽  
Mark J. Shelton ◽  
Yu Lou ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Subjects ◽  
Open Label ◽  
Time Curve ◽  
Once Daily ◽  
Open Label Study ◽  
Label Study ◽  
Concentration Time

ABSTRACT Plasma ketoconazole (KETO), amprenavir (APV), and ritonavir (RTV) pharmacokinetics were evaluated in 15 healthy subjects after being treated with KETO at 200 mg once daily (QD), fosamprenavir (FPV)/RTV at 700/100 mg twice daily (BID), and then KETO at 200 mg QD plus FPV/RTV at 700/100 mg BID in this open-label study. The KETO area under the concentration-time curve at steady state was increased 2.69-fold with FPV/RTV. APV exposure was unchanged, and RTV exposure was slightly increased.

PSX-A-27 Late-Breaking: The sulfatase mediated regeneration of androstenone from androstenone sulfate in boar fat

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 376-376
Author(s):  
Christine Bone ◽  
E James Squires
Keyword(s):  
Leydig Cells ◽  
High Performance ◽  
Boar Taint ◽  
Pork Products ◽  
Significant Difference ◽  
Sulfatase Activity ◽  
Steroid Sulfate ◽  
Student’S T ◽  
Entire Male ◽  
Student’S T Test

Abstract Boar taint is an off-odour or off-flavour that develops in heated pork products from entire male pigs, which is caused by the accumulation of androstenone, a sex pheromone, in the fat. However, we have previously demonstrated that a significant amount of androstenone undergoes sulfoconjugation upon synthesis in the Leydig cells and circulates in the plasma primarily as a polar steroid sulfate. Therefore, the purpose of this study was to determine if androstenone sulfate can be deconjugated within the adipose tissue by the sulfatase enzyme to return free androstenone and indirectly contribute to the development of boar taint. Backfat was obtained from 6-month-old terminal cross [Duroc x (Landrace x Yorkshire)] boars that had high (n=4) or low (n=4) sulfatase expression as determined by RT-PCR. Sulfatase activity in the fat was measured by quantifying the conversion of androstenone sulfate to free androstenone. Backfat was homogenized and the supernatant was incubated with [3H]-androstenone sulfate for 24-hours. Androstenone was extracted from the incubation using ether and steroid conversion was quantified using high-performance liquid chromatography (HPLC). Additionally, fat androstenone concentrations were quantified using an established HPLC procedure. Statistical analysis was conducted using a Student’s t-test. There was a significant difference (p=0.04) in the expression of sulfatase between the high (2.99 ± 0.67) and low (1.21 ± 0.19) sulfatase boars and the percentage of androstenone sulfate that was converted to free androstenone was proportional to the expression of sulfatase. Interestingly, the expression of sulfatase was positively related to the concentration of androstenone in the fat in boars with high sulfatase expression; however, this relation was not as strong in animals with low sulfatase expression. These preliminary results suggest that the development of boar taint may occur indirectly through the deconjugation of androstenone sulfate in boars with high expression of sulfatase in the fat.

scholarly journals Lack of Effect of Zafirlukast on the Pharmacokinetics of Azithromycin, Clarithromycin, and 14-Hydroxyclarithromycin in Healthy Volunteers

1999 ◽  
Vol 43 (5) ◽  
pp. 1152-1155 ◽  
Author(s):  
Kevin W. Garey ◽  
Charles A. Peloquin ◽  
Paul G. Godo ◽  
Anne N. Nafziger ◽  
Guy W. Amsden
Keyword(s):  
Steady State ◽  
Healthy Subjects ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Steady State Concentration ◽  
Open Label ◽  
Time Curve ◽  
Data Analyses ◽  
Concentration Time ◽  
State Concentration

ABSTRACT This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems. Data analyses were done by noncompartmental and nonparametric methods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC. While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC.

The Pharmacokinetics of Loratadine in Normal Geriatric Volunteers

1988 ◽  
Vol 16 (1) ◽  
pp. 50-60 ◽  
Author(s):  
J. Hilbert ◽  
V. Moritzen ◽  
A. Parks ◽  
E. Radwanski ◽  
G. Perentesis ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
High Performance ◽  
The Elderly ◽  
Maximum Plasma Concentration ◽  
Pharmacokinetic Analysis ◽  
Maximum Plasma ◽  
Open Label ◽  
Post Dose ◽  
Time Curve ◽  
Concentration Time

The pharmacokinetics of loratadine, a non-sedating anti-histamine, were studied in 12 normal geriatric volunteers. In an open label fashion, each volunteer received one 40 mg loratadine capsule. Blood was collected prior to and at specified times (up to 120 h) after dosing. Plasma loratadine concentrations were determined by a specific radioimmunoassay and those of an active metabolite, descarboethoxyloratadine, by high performance liquid chromatography. Concentrations of loratadine in the disposition phase were fitted to a biexponential equation and those of descarboethoxyloratadine to either a monoexponential or biexponential equation for pharmacokinetic analysis. Loratadine was rapidly absorbed, reaching a maximum plasma concentration of 50.5 ng/ml at 1.5 h after dosing. The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively. The area under the plasma concentration–time curve, was 146.7 h·ng/ml. Descarboethoxyloratadine had a maximum plasma concentration of 28.0 ng/ml at 2.9 h post-dose and an area under the concentration–time curve of 394.9 h·ng/ml. Its disposition half-lives in the distribution and elimination phases were 2.8 and 17.4 h, respectively. Comparison of these data with those from a previous study of loratadine in young adults showed no clear differences in the disposition half-lives between the two groups. The clearance of loratadine tends to be lower in the elderly, but inter-individual variation within each age group appears greater than any age effect.

Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat

2002 ◽  
Vol 97 (5) ◽  
pp. 1218-1226 ◽  
Author(s):  
Diederik K. Van Sassenbroeck ◽  
Peter De Paepe ◽  
Frans M. Belpaire ◽  
Paul A. Boon ◽  
Walter A. Buylaert
Keyword(s):  
Blood Pressure ◽  
High Performance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Control Procedure ◽  
Time Data ◽  
Time Curve ◽  
Concentration Time ◽  
Gamma Hydroxybutyrate ◽  
Significant Difference

Background Hypovolemia alters the effect of propofol in the rat by influencing the pharmacokinetics and the end organ sensitivity. We now studied the effect of hypovolemia on the anesthetic gamma-hydroxybutyrate (GHB) because in contrast with propofol it increases blood pressure. Methods Thirty-two rats were randomly assigned to undergo moderate hypovolemia or a control procedure. Each rat received either an infusion of sodium-GHB (390 mg x kg(-1) x 5 min(-1)) or the same volume of an equimolar solution of sodium chloride (6.9%). Plasma samples were taken for GHB assay (high-performance liquid chromatography) and the electroencephalography and blood pressure values were recorded. A two-compartment model with Michaelis-Menten elimination was fitted to the concentration-time data and a sigmoid E(max) model to the electroencephalographic effect effect site concentration curve allowing the study of the end organ sensitivity. Results Plasma concentration-time curves and the total volume of distribution in hypovolemic and normovolemic rats were comparable with only small but significant differences in central volume of distribution and the intercompartmental clearance. There was no significant difference either in the distribution from the plasma to the brain (k(e0)) or in the end organ sensitivity (EC50 = 335 +/- 76 microg/ml in control vs. 341 +/- 89 microg/ml in hypovolemic rats). GHB temporarily increased mean arterial pressure in both groups, which cannot be explained by the sodium salt alone. Conclusions Hypovolemia does not influence the overall concentration-time curve of GHB and induces no changes in the electroencephalographic effect of GHB in the rat. This difference with propofol may be due to the fact that it increases blood pressure but also due to its different pharmacokinetic properties.

scholarly journals Sequential Open-Label Study of the Safety, Tolerability, and Pharmacokinetic Interactions between Dihydroartemisinin-Piperaquine and Mefloquine in Healthy Thai Adults

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Borimas Hanboonkunupakarn ◽  
Rob W. van der Pluijm ◽  
Richard Hoglund ◽  
Sasithon Pukrittayakamee ◽  
Markus Winterberg ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistant ◽  
Combination Therapies ◽  
Open Label ◽  
Time Curve ◽  
Open Label Study ◽  
Label Study ◽  
Content Type ◽  
Concentration Time ◽  
Pharmacokinetic Properties

ABSTRACT Artemisinin-based combination therapies (ACTs) have contributed substantially to the global decline in Plasmodium falciparum morbidity and mortality, but resistance to artemisinins and their partner drugs is increasing in Southeast Asia, threatening malaria control. New antimalarial compounds will not be generally available soon. Combining three existing antimalarials in the form of triple ACTs, including dihydroartemisinin (DHA)-piperaquine + mefloquine, is a potential treatment option for multidrug-resistant Plasmodium falciparum malaria. In a sequential open-label study, healthy Thai volunteers were treated with DHA-piperaquine (120 to 960 mg), mefloquine (500 mg), and DHA-piperaquine + mefloquine (120 to 960 mg + 500 mg), and serial symptom questionnaires, biochemistry, full blood counts, pharmacokinetic profiles, and electrocardiographic measurements were performed. Fifteen healthy subjects were enrolled. There was no difference in the incidence or severity of adverse events between the three treatment arms. The slight prolongation in QTc (QT interval corrected for heart rate) associated with DHA-piperaquine administration did not increase after administration of DHA-piperaquine + mefloquine. The addition of mefloquine had no significant effect on the pharmacokinetic properties of piperaquine. However, coadministration of mefloquine significantly reduced the exposures to dihydroartemisinin for area under the concentration-time curve (−22.6%; 90% confidence interval [CI], −33.1, −10.4; P = 0.0039) and maximum concentration of drug in serum (−29.0%; 90% CI, −40.6, −15.1; P = 0.0079). Mefloquine can be added safely to dihydroartemisinin-piperaquine in malaria treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT02324738.)

Effect of dosing interval on pharmacokinetics of fentanyl pectin nasal spray from a crossover study

2015 ◽  
Vol 11 (2) ◽  
pp. 139 ◽  
Author(s):  
Cuiping Chen, PhD ◽  
Shay Bujanover, MD ◽  
Anita Gupta, DO, PharmD
Keyword(s):  
Nasal Spray ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Time Curve ◽  
Open Label Study ◽  
Concentration Time ◽  
The Difference ◽  
Multiple Dose Pharmacokinetics ◽  
The Right ◽  
Dosing Intervals

Objective: To evaluate the effects of different dosing intervals on multiple-dose pharmacokinetics, and safety and tolerability of fentanyl pectin nasal spray (FPNS).Methods: This was an open-label study in healthy volunteers. Five FPNS treatments (1 × 100 μg; 2 × 100 μg at 4-, 2-, and 1-hour intervals, and 8 × 100 μg consecutively) were administered to the right nostril, with a ≥3-day washout period. Blood samples were collected at predose and up to 1,440 minutes postdose. Plasma fentanyl concentrations were determined. Pharmacokinetic parameters—peak concentration (Cmax), time to Cmax (tmax), and area under the concentration-time curve (AUC)—were derived using noncompartmental method. For the two-dose regimens, pharmacokinetic parameters were compared between doses using a paired t-test with p < 0.05 as statistically significant.Results: Thirteen subjects were enrolled and 10 completed the study. Median tmax was 10-15 minutes across five regimens. Cmax post the second dose significantly increased for 1-hour (p < 0.0001) and 2-hour (p < 0.001) but not 4-hour intervals (p = 0.462). Cmax and AUC0-24 following 8 × 100 μg were approximately fivefold of those following 1 × 100 μg. Dizziness (11.9 percent) and somnolence (4.9 percent) were most common adverse events (AEs). 12.9 percent of patients discontinued due to AEs.Conclusions: FPNS exhibited consistently rapid tmax. When intervals between two doses were shorter, the difference in Cmax between the first and second dose was larger. All regimens of FPNS were well tolerated. Exposure reached a plateau after eight consecutive doses, suggesting potential limited absorption through the nasal mucosa.

scholarly journals ASSOCIATION BETWEEN SERUM URIC ACID AND METABOLIC SYNDROME

2018 ◽  
Vol 11 (10) ◽  
pp. 400 ◽  
Author(s):  
Thaslima Nandhini Js ◽  
Savitha Basker G ◽  
Vishnupriya V
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Venous Blood ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Serum Triglycerides ◽  
Significant Difference ◽  
Disease Condition ◽  
Student’S T ◽  
Student’S T Test

Objective: Metabolic syndrome is a cluster of disease condition characterized by truncal obesity, hypertriglyceridemia, elevated blood pressure, and insulin resistance. An excessive circulating uric acid (UA) level even within normal range is always comorbid with metabolic syndrome and its components. The aim of the current study was to investigate the association between metabolic syndrome and serum UA level.Methods: A total of 60 subjects were divided into two groups of healthy (30 individuals) and metabolic syndrome patients (30 individuals) from dental outpatient department of Saveetha Dental College and Hospitals. 5 ml of fasting venous blood was collected in the plain collection tubes and centrifuged, and then serum was separated. Then, the serum was used to analyze the fasting blood glucose, serum triglycerides (TGLs), and serum UA by GOD-POD, enzymatic colorimetric, and uricase method, respectively. A statistical analysis was performed using Student’s t-test. p<0.05 was considered to be statistically significant.Result: Mean body mass index (BMI), fasting blood sugar (FBS), TGL, and UA level of control group were 23.36±1.81, 84.45±13.1, 110.9±22.6, and 3.48±1.21 respectively. Mean BMI, FBS, TGL, and UA level of study group were 35.24±3.04, 122.85±23.3, 212.1±39.6 and 9.08±2.63 respectively. There is a significant difference between these two groups with p<0.0001.Conclusion: This study showed that those individuals with metabolic syndrome have higher UA level that indicates hyperuricemia which is a significant predictor of metabolic syndrome.

scholarly journals Pharmacokinetic Interactions between the Hormonal Emergency Contraception, Levonorgestrel (Plan B), and Efavirenz

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Monica L. Carten ◽  
Jennifer J. Kiser ◽  
Awewura Kwara ◽  
Samantha Mawhinney ◽  
Susan Cu-Uvin
Keyword(s):  
Geometric Mean ◽  
Liver Function Tests ◽  
Open Label ◽  
Time Curve ◽  
Geometric Means ◽  
Concentration Time ◽  
Plan B ◽  
Effective Contraception ◽  
Grade 3 ◽  
Hiv Negative

Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV).Design. Prospective, open-label, single-arm, equivalence study.Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters.T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed.Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng*hr/mL, and maximum concentration (Cmax⁡) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities.Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV.

scholarly journals Effect of the ketoprofen on the preemptive analgesia in female cats undergoing to ovariohysterectomy

Revista CERES ◽  
2017 ◽  
Vol 64 (1) ◽  
pp. 18-24
Author(s):  
Dayvid Vianêis Farias de Lucena ◽  
Fernanda Vieira Henrique ◽  
Amara Gyane Alves de Lima ◽  
Almir Pereira de Souza ◽  
Pedro Isidro da Nóbrega Neto
Keyword(s):  
Statistical Analysis ◽  
Preemptive Analgesia ◽  
Pain Scores ◽  
Significant Difference ◽  
Reduction Of Pain ◽  
Baseline Values ◽  
Student’S T ◽  
Level Of Significance ◽  
Postoperative Administration ◽  
Student’S T Test

ABSTRACT The objective of this study was to investigate the effect of the ketoprofen on the preemptive analgesia in female cats submitted to ovariohysterectomy. Sixteen healthy cats were distributed into two groups, with eight animals each, by means of a draw, in a preemptive group (PREG), in which the animal received ketoprofen (1 mg/kg) subcutaneously two hours before the surgery; and postsurgery group (POSG), in which ketoprofen (1 mg/kg) was administered subcutaneously immediately after surgery. In both groups, ketoprofen was given 24, 48 and 72 hours after the first adminstration. Heart and respiratory frequencies and glycemia were measured in all animals during the days first ten postsurgery. Analgesia was measured by assigning scores at zero, two, four, six, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after the surgical procedure. Statistical analysis was performed using two-way analysis of variance followed by Tukey's test to compare the moments and Student's t-test for comparison between groups. Pain scores were evaluated using test of U-Mann-Withney or Kruskall-Wallis, all at the 5% level of significance. Pain scores were significantly lower in PREG in M0, M6, M72, M96 and M120. No significant difference was found in the levels of glycemia in comparison to baseline values. Ketoprofen promotes postsurgery analgesia in female cats submitted to ovariohysterectomy and preemptive and postsurgery administration provides an earlier reduction of pain scores when compared to postoperative administration, only.

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