Bioequivalence of Two Methotrexate Formulations in Psoriatic and Cancer Patients

1993 ◽  
Vol 27 (12) ◽  
pp. 1434-1438 ◽  
Author(s):  
Mary E. Teresi ◽  
Charles E. Riggs ◽  
Paul M. Webster ◽  
Michael J. Adams ◽  
Patrick K. Noonan ◽  
...  
Keyword(s):  
Peak Concentration ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
University Hospital ◽  
Brand Name ◽  
Mean Values ◽  
Time To Peak ◽  
Clinical Research Center ◽  
Percent Rate ◽  
Randomized Crossover Study

OBJECTIVE: To compare the bioequivalence of a generic methotrexate (MTX) tablet (Mylan) with that of a brand-name (Lederle) product. DESIGN: A single-dose, randomized, crossover study. SETTING: Clinical Research Center (CRC) at a university hospital. PATIENTS: Men and women who had a diagnosis of malignancy or psoriasis who were at least 21 years old. METHODOLOGY: Two overnight study periods were scheduled at the CRC at least one week, but not more than two weeks apart. Each period consisted of a 10-hour fast prior to and 4 hours following oral MTX 15 mg administered as six 2.5-mg tablets. Blood samples were collected over 48 hours. Plasma MTX concentrations were determined using an HPLC assay. Area under the curve from zero to infinity (AUC0-∞) was calculated by the log-trapezoidal method. RESULTS: Twenty-two patients (21 psoriasis, 1 colon cancer) aged 23–61 years completed both study periods. Mean values for peak concentration, time to peak concentration, and AUC0-∞ were 0.80 μmol/L, 1.2 hours, and 3.0 μmol•h/L, respectively, for Mylan's MTX tablets and 0.81 μmol/L, 1.4 hours, 3.0 μmol•h/L, respectively, for Lederle's MTX. Normalization for weight or body surface area did not affect interpatient variability. Relative bioavailability of generic MTX was 99.2 percent Rate and extent of absorption were not significantly different and the confidence intervals were within the range of 80–120 percent required by the Food and Drug Administration. CONCLUSIONS: Mylan's MTX tablet is bioequivalent to Lederle's product.

scholarly journals Effect of Grapefruit Juice on Clarithromycin Pharmacokinetics

1998 ◽  
Vol 42 (4) ◽  
pp. 927-929 ◽  
Author(s):  
Kit L. Cheng ◽  
Anne N. Nafziger ◽  
Charles A. Peloquin ◽  
Guy W. Amsden
Keyword(s):  
Crossover Study ◽  
Healthy Subjects ◽  
Peak Concentration ◽  
Grapefruit Juice ◽  
Pharmacokinetic Parameters ◽  
Time To Peak ◽  
Before And After ◽  
Randomized Crossover Study

ABSTRACT To investigate whether grapefruit juice inhibits the metabolism of clarithromycin, 12 healthy subjects were given water or grapefruit juice before and after a clarithromycin dose of 500 mg in a randomized crossover study. Administration of grapefruit juice increased the time to peak concentration of both clarithromycin (82 ± 35 versus 148 ± 83 min; P = 0.02) and 14-hydroxyclarithromycin (84 ± 38 min versus 173 ± 85;P = 0.01) but did not affect other pharmacokinetic parameters.

scholarly journals Naloxone and nalmefene absorption delivered by hollow microneedles compared to intramuscular injection

2021 ◽  
Author(s):  
Mark G. Papich ◽  
Roger J. Narayan
Keyword(s):  
Peak Concentration ◽  
Plasma Sample ◽  
Area Under The Curve ◽  
Mass Spectrometry Detection ◽  
Plasma Analysis ◽  
Future Studies ◽  
Time To Peak ◽  
Hollow Microneedle ◽  
The Mean ◽  
Epaxial Muscles

Abstract Naloxone and nalmefene were administered to seven research Beagle dogs, (mean weight approximately 12 kg) at a dose of 0.04 mg/kg and 0.014 mg/kg for naloxone and nalmefene, respectively. Each dose was administered intramuscularly (IM) with a standard IM injection and with a hollow microneedle device array using needles of 1 mm in length. The IM injection was delivered in the epaxial muscles, and the microneedle injection was delivered in the skin over the shoulder of each dog. Each dog received the same injections in a cross-over design. Following the injection, blood samples were collected for plasma analysis of naloxone and nalmefene by high pressure liquid chromatography with mass spectrometry detection (LCMS). The plasma sample concentrations were plotted for observed patterns of absorption and analyzed with non-compartmental pharmacokinetic methods (NCA). The results showed that the injection of naloxone from the microneedle device produced a higher peak concentration (CMAX) by 2.15x compared the IM injection of the same dose, and time to peak concentration (TMAX) was similar. For the nalmefene injection, the peak was not as high (lower CMAX) by 0.94x for the microneedle injection compared to the IM injection of the same dose. The microneedle produced an exposure, measured by area under the curve (AUC)) that was 0.85x and 0.58x as high for naloxone and nalmefene, respectively, than the injection by the IM route. We also observed that although the dose for naloxone was approximately 3x higher for naloxone compared to nalmefene, the mean peak concentration achieved from the naloxone injection was more than 12x higher than the nalmefene injection. These studies were designed to test the feasibility of using the hollow microneedle array as an effective method of naloxone and nalmefene delivery for emergency treatment of opioid-induced respiratory depression (OIRD). The results of these studies will form the basis of future studies, using the dog as a model, for development of hollow microneedle microarray devices to deliver opioid antagonists for treatment of OIRD in people.

scholarly journals Comparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability

2021 ◽  
Vol 14 (1) ◽  
pp. 35
Author(s):  
Natasha N. Bondareva Williams ◽  
Taylor Russell Ewell ◽  
Kieran Shay Struebin Abbotts ◽  
Kole Jerel Harms ◽  
Keith A. Woelfel ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Body Composition ◽  
Peak Concentration ◽  
Area Under The Curve ◽  
Peak Frequency ◽  
Fat Free Mass ◽  
Time To Peak ◽  
Adult Humans ◽  
The Relationship

Data supporting the physiological effects of cannabidiol (CBD) ingestion in humans are conflicting. Differences between CBD preparations and bioavailability may contribute to these discrepancies. Further, an influence of body composition on CBD bioavailability is feasible, but currently undocumented. The aims of this study were to: (1) compare the pharmacokinetics of five oral CBD preparations over 4 h; (2) examine the relationship between body composition and CBD pharmacokinetics; and, (3) explore the influence of CBD on heart rate variability. In total, five preparations of CBD, standardized to 30 mg, were orally administered to 15 healthy men and women (21–62 years) in a randomized, crossover design. Prior to and 60 min following CBD ingestion, heart rate variability was determined. Body composition was assessed using dual energy X-ray absorptiometry. Peak circulating CBD concentration, time to peak concentration, and area under the curve was superior in a preparation comprising 5% CBD concentration liquid. Fat free mass was a significant predictor (R2 = 0.365, p = 0.017) of time to peak concentration for this preparation. Several heart rate variability parameters, including peak frequency of the high frequency band, were favorably, but modestly modified following CBD ingestion. These data confirm an influence of CBD preparation and body composition on CBD bioavailability, and suggest that acute CBD ingestion may have a modest influence on autonomic regulation of heart rate.

scholarly journals Effect of Fat and Fasting on Post-Prandial Relative Bioavailability of Vitamin E

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1797-1797
Author(s):  
Ifechukwude Ebenuwa ◽  
Pierre-Christian Violet ◽  
Hongbin Tu ◽  
Mark Levine
Keyword(s):  
Vitamin E ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Breakfast Meal ◽  
Healthy Women ◽  
Funding Sources ◽  
Clinical Research Center ◽  
Serial Sampling ◽  
Group 12 ◽  
Fast Group

Abstract Objectives We hypothesized that meal fat co-administered with fat-soluble α-tocopherol (vitamin E) facilitates vitamin E absorption and increases relative bioavailability in the immediate post-prandial phase, when compared with non-fat meals. We tested this hypothesis using deuterated oral α-tocopherol co-administered with breakfast containing meal fat (40% group) and without meal fat (0% group) in hospitalized healthy women. We also evaluated the role of subsequent meals in modulating the vitamin E relative bioavailability by fasting patients for 12 h following a breakfast meal with 0% fat (0% fat-fasting group). We compared area under the curve (AUC) for oral d3-α-tocopherols %enrichment at 0–4 h, 0–12 h and 0–24 h. Methods Custom-synthesized deuterated d3-α-tocopherol was co-administered with breakfast meal with and without fat, with subsequent serial sampling. Enrolled subjects were healthy women hospitalized for 5–6 days at the NIH Clinical Research Center. Results The AUC0–4 h for 40% fat group was more than twice 0% fat group (6.4 ± 1.8 vs 2.3 ± 0.7). This difference was erased following ingestion of meals containing 30% fat at 4 h and 8 h post-dosing, with AUC0–12 h for 40% and 0% fat groups (96.8 ± 10.2 vs 107.4 ± 8.) and AUC0–24 h (254 ± 16.3 vs 301.8 ± 19.7). To evaluate the effect of fasting, we compared 0% fat group with 0% fat-fast groups. At 4 h and 8 h post-dosing, the 0% fat group received meals with 30% fat, while 0% fat-fast group remained in fasting state. We therefore predicted and found significantly higher AUC0–12 h in the 0% fat group compared with the 0% fat-fast (107.4 ± 8.1 vs 41.1 ± 5.2 P < 0.001). Following meal consumption by 0% fat-fast group 12 h post-dosing, AUC0–24 h between 0% fat and 0% fat-fast groups narrowed but remained significantly different (301.8 ± 19.7 vs 207.4 ± 10.6, P < 0.002) respectively. Conclusions Findings demonstrate the effect of meal fat in facilitating vitamin E absorption in the immediate post-prandial state, resulting in increased relative bioavailability. Conversely, fasting decreases vitamin E relative bioavailability. Funding Sources NIDDK Intramural Program.

Bioavailability and Patient Acceptance of Cyclosporine Soft Gelatin Capsules in Renal Allograft Recipients

1992 ◽  
Vol 26 (2) ◽  
pp. 175-179 ◽  
Author(s):  
David I. Min ◽  
George C. Hwang ◽  
Susan Bergstrom ◽  
Peter N. Madras ◽  
David Shaffer ◽  
...  
Keyword(s):  
Peak Concentration ◽  
Renal Allograft ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Oral Solution ◽  
Patient Acceptance ◽  
Gelatin Capsule ◽  
Blood Concentrations ◽  
Blood Samples ◽  
Soft Gelatin Capsule

OBJECTIVE: To evaluate the relative bioavailability and patient acceptance of cyclosporine (CSA) soft gelatin capsule versus oral solution in renal allograft recipients. DESIGN, SETTING, AND PATIENTS: The bioavailability of CSA capsules was compared with that of CSA solution with crossover study design in the outpatient clinic setting. Nine renal allograft recipients with stable renal function participated in this study. METHODS: CSA dose was switched from solution to capsule in each patient for seven days. At steady-state, nine blood samples were obtained over a 12-hour period from each patient on day 7 for CSA solution and on day 14 for CSA capsules. CSA blood samples were analyzed by HPLC and fluorescence polarization immunoassay (FPIA) methods. Time to peak concentration (Tmax), peak concentration (Tmax), and area under the curve (AUC) were calculated on days 7 and 14, and compared using the matched Student's t-test. Patient acceptance was evaluated by patient preference on the questionnaire. RESULTS: For CSA blood concentrations measured by HPLC assay, the Tmax, Cmax, and AUC were 3.4 ± 1.3 h, 569 ± 240 nmol/L, and 4659 ± 2144 h • nmol/L (mean ± SD), respectively, with solution and 4.2 ± 2.1 h, 560 ± 257 nmol/L, and 4765 ± 1799 h • nmol/L (mean ± SD), respectively, with capsules. These differences were not significant (p>0.1). The bioavailability was not significantly different between capsules and solutions when it was measured by PFIA assay (p>0.1). The mean (± SD) relative bioavailability of capsules compared with solution was 109 ± 29 percent AUC (0–12 h) measured by HPLC and 111 ± 27 percent AUC (0–12 h) measured by FPIA. All patients expressed preference for capsules over the solution. CONCLUSIONS: CSA oral soft gelatin capsule is bioequivalent to CSA oral solution and most patients preferred the capsule to the oral solution.

scholarly journals Decreased exercise capacity in young athletes using self-adapted mouthguards

2021 ◽  
Author(s):  
Johannes Lässing ◽  
Roberto Falz ◽  
Antina Schulze ◽  
Christoph Pökel ◽  
Maximilian Vondran ◽  
...  
Keyword(s):  
Blood Lactate ◽  
Maximum Load ◽  
Body Plethysmography ◽  
Con A ◽  
Young Athletes ◽  
Exercise Tests ◽  
Mean Values ◽  
The Mean ◽  
Preventive Effects ◽  
Randomized Crossover Study

Abstract Purpose There is evidence of both the preventive effects and poor acceptance of mouthguards. There are various effects on performance depending on the type of mouthguard model. Hemodynamic responses to wearing a mouthguard have not been described. The aim of this study was to investigate the effects of self-adapted mouthguards with breathing channels (SAMGvent). Methods In this randomized crossover study, 17 healthy, active subjects (age 25.12 ± 2.19 years) underwent body plethysmography and performed two incremental exertion tests wearing a (SAMGvent) and not wearing (CON) a mouthguard. Blood lactate, spirometrics, and thoracic impedance were measured during these maximum exercise tests. Results The mean values using a SAMGvent revealed significantly greater airway resistance compared to CON (0.53 ± 0.16 kPa·L−1 vs. 0.35 ± 0.10 kPa·L−1, respectively; p = < 0.01). At maximum load, ventilation with SAMGvent was less than CON (118.4 ± 28.17 L min−1 vs. 128.2 ± 32.16 L min−1, respectively; p = < 0.01). At submaximal loads, blood lactate responses with SAMGvent were higher than CON (8.68 ± 2.20 mmol·L−1 vs. 7.89 ± 1.65 mmol·L−1, respectively; p < 0.01). Maximum performance with a SAMGvent was 265.9 ± 59.9 W, and without a mouthguard was 272.9 ± 60.8 W (p < 0.01). Maximum stroke volume was higher using a SAMGvent than without using a mouthguard (138.4 ± 29.9 mL vs. 130.2 ± 21.2 mL, respectively; p < 0.01). Conclusion Use of a self-adapted mouthguard led to increased metabolic effort and a significant reduction in ventilation parameters. Unchanged oxygen uptake may be the result of cardiopulmonary compensation and increased breathing efforts, which slightly affects performance. These results and the obvious preventive effects of mouthguards support their use in sports.

scholarly journals Characterization of the thrombin generation profile in systemic lupus erythematosus

2017 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
A Kern ◽  
E Barabás ◽  
A Balog ◽  
Sz Burcsár ◽  
M Kiszelák ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
Time To Peak ◽  
Cat Assay ◽  
Coagulation Tests ◽  
Healthy Control

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

scholarly journals Early prediction of hospital admission for emergency department patients: a comparison between patients younger or older than 70 years

2017 ◽  
Vol 35 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Jacinta A Lucke ◽  
Jelle de Gelder ◽  
Fleur Clarijs ◽  
Christian Heringhaus ◽  
Anton J M de Craen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Hospital Admission ◽  
Older Patients ◽  
Prediction Models ◽  
Age Groups ◽  
Vital Signs ◽  
Area Under The Curve ◽  
University Hospital ◽  
Multivariable Logistic Regression Analysis ◽  
Younger Patients

ObjectiveThe aim of this study was to develop models that predict hospital admission to ED of patients younger and older than 70 and compare their performance.MethodsPrediction models were derived in a retrospective observational study of all patients≥18 years old visiting the ED of a university hospital during the first 6 months of 2012. Patients were stratified into two age groups (<70 years old and ≥70 years old). Multivariable logistic regression analysis was used to identify predictors of hospital admission among factors available immediately after patient arrival to the ED. Validation of the prediction models was performed on patients presenting to the ED during the second half of the year 2012.Results10 807 patients were included in the derivation and 10 480 in the validation cohorts. The strongest independent predictors of hospital admission among the 8728 patients <70 years old were age, sex, triage category, mode of arrival, performance of blood tests, chief complaint, ED revisit, type of specialist, phlebotomised blood sample and all vital signs. The area under the curve (AUC) of the validation cohort for those <70 years old was 0.86 (95% CI 0.85 to 0.87). Among the 2079 patients ≥70 years, the same factors were predictive, except for gender, type of specialist and heart rate; the AUC was 0.77 (95% CI 0.75 to 0.79). The prediction models could identify a group of 10% of patients with the highest risk in whom hospital admission was predicted at ED triage, with a positive predictive value (PPV) of 71% (95% CI 68% to 74%) in younger patients and PPV of 87% (95% CI 81% to 92%) in older patients.ConclusionDemographic and clinical factors readily available early in the ED visit can be useful in identifying patients who are likely to be admitted to the hospital. While the model for the younger patients had a higher AUC, the model for older patients had a higher PPV in identifying the patients at highest risk for admission. Of note, heart rate was not a useful predictor in the older patients.

scholarly journals Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.

1996 ◽  
Vol 40 (7) ◽  
pp. 1617-1622 ◽  
Author(s):  
J E Conte ◽  
J Golden ◽  
S Duncan ◽  
E McKenna ◽  
E Lin ◽  
...  
Keyword(s):  
Single Dose ◽  
Bronchoalveolar Lavage ◽  
Peak Concentration ◽  
Area Under The Curve ◽  
Lavage Fluid ◽  
Diffusion Method ◽  
Alveolar Cells ◽  
Epithelial Lining Fluid ◽  
Drug Concentrations ◽  
Oral Doses

The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was present in ELF. The correlation of these kinetic observations with clinical efficacy or toxicity was not investigated and is unclear, but the data provide a basis for further kinetic and clinical studies.

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