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.

Pharmacokinetics of Inhaled Liposome-encapsulated Fentanyl

1995 ◽  
Vol 83 (2) ◽  
pp. 277-284. ◽  
Author(s):  
Orlando R. Hung ◽  
Sara C. Whynot ◽  
John R. Varvel ◽  
Stephen L. Shafer ◽  
Michael Mezei
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Administration ◽  
Venous Blood ◽  
Volume Of Distribution ◽  
Sustained Drug Release ◽  
Future Studies ◽  
Time To Peak ◽  
Drug Molecules ◽  
Peak Absorption ◽  
The Mean

Background Pulmonary administration of fentanyl solution can provide satisfactory but brief postoperative pain relief. Liposomes are microscopic phospholipid vesicles that can entrap drug molecules. Liposomal delivery of fentanyl has the potential to control the uptake of fentanyl by the lungs and thus provide sustained drug release. To demonstrate that inhalation of a mixture of free and liposome-encapsulated fentanyl can provide a rapid increase and sustained plasma fentanyl concentrations (CfenS), this study determined the pharmacokinetic profiles after the inhalation of free and liposome-encapsulated fentanyl in healthy volunteers. Methods After obtaining institutional approval and informed consent, ten healthy volunteers (five men, five women) were studied. Each subject received 200 micrograms intravenous fentanyl and inhaled 2,000 micrograms of free (50%) and liposome-encapsulated fentanyl (50%) on separate occasions. Frequent venous blood samples were collected, and CfenS were determined by radioimmunoassay. The pharmacokinetics and absorption characteristics of the inhaled mixture of free and liposome-encapsulated fentanyl were determined using moment analysis and least-squares numeric deconvolution. Results The mean (+/- SD) volume of distribution at steady-state and clearance of fentanyl after the intravenous administration were comparable to previous studies: 435 +/- 1821 and 0.584 +/- 0.209 l.min-1, respectively. The mean (+/- SD) peak Cfen was significantly greater for the intravenous administration compared to the aerosol mixture of free and liposome-encapsulated fentanyl (4.67 +/- 1.87 vs. 1.15 +/- 0.36 ng.ml-1). However, CfenS at 8 and 24 h after aerosol administration were greater compared to intravenous (0.25 +/- 0.14 and 0.12 +/- 0.16 ng.ml-1 for aerosol versus 0.16 +/- 0.10 and 0.05 +/- 0.06 ng.ml-1 for intravenous). The peak absorption rate, time to peak absorption, and bioavailability after inhalation were 7.02 (+/- 2.34) micrograms.min, -1(16) (+/- 8.0) min, and 0.12 (+/- 0.11), respectively. Conclusions The data suggest that this analgesic method offers a simple and noninvasive route of administration with a rapid increase of Cfen and a prolonged therapeutic fentanyl concentration. Future studies are required to determine the optimal liposome composition that would produce a sustained stable Cfen within analgesic therapeutic concentrations.

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.

Bioavailability of Temazepam: Comparison of Four 7.5-mg Capsules with a Single 30-mg Capsule

1993 ◽  
Vol 27 (6) ◽  
pp. 695-699 ◽  
Author(s):  
Craig Abolin ◽  
Dar-Shong Hwang ◽  
Frank Mazza
Keyword(s):  
Peak Concentration ◽  
Dosage Form ◽  
Peak Plasma ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Latin Square ◽  
Open Label ◽  
Time To Peak ◽  
Rate Of Absorption ◽  
The Mean

OBJECTIVE: To compare the bioavailability of four temazepam 7.5-mg capsules (Restoril, Sandoz Pharmaceuticals) with that of a single temazepam 30-mg capsule. DESIGN: Single-dose, open-label, two-period, crossover (replicated Latin square). SETTING: Domiciled environment for clinical testing. PARTICIPANTS: Twenty-six healthy male volunteers aged 18–40 years; 25 completed the study. INTERVENTIONS: Subjects randomly received either four temazepam 7.5-mg capsules or one temazepam 30-mg capsule. Blood samples were drawn at various time points after each period (0-48 h), and analyzed for plasma concentration of temazepam. The washout period between doses was five days. MAIN OUTCOME MEASUREMENTS: Five parameters of both dosage forms were compared: (1) area under curve (AUC), (2) peak concentration (Cmax), (3) time to peak concentration (Tmax), (4) apparent rate constant for absorption, and (5) lag time for appearance of drug in plasma. Statistical procedures included ANOVA, power analysis, and confidence limits. RESULTS: The mean AUC for the four 7.5-mg capsules and one 30-mg capsule differed by less than 2 percent and the mean Cmax differed by less than 14 percent for the two dosage strengths; neither of these differences reached statistical significance (p>0.05). The 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form (mean Tmax 1.18 and 1.73 h, respectively; p=0.01). CONCLUSIONS: The two formulations of temazepam were bioequivalent with respect to the extent of bioavailability. Regarding the rate of absorption, however, the 7.5-mg capsules reached peak plasma concentrations significantly faster than the 30-mg dosage form.

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.

Left Ventricular Dysfunction and Blood Glycohemoglobin Levels in Young Diabetics

1991 ◽  
Vol 30 (05) ◽  
pp. 183-188
Author(s):  
A. Aydrner ◽  
A. Oto ◽  
E. Oram ◽  
O. Gedik ◽  
C. F. Bekdik ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Filling Fraction ◽  
Time To Peak ◽  
Significant Difference ◽  
The Mean ◽  
Hba1c Levels

Left ventricular function including regional wall motion (RWM) was evaluated by 99mTc first-pass and equilibrium gated blood pool ventriculography and glycohemoglobin (HbA1c) blood levels determined by a quantitative column technique in 25 young patients with insulin-dependent diabetes mellitus without clinical evidence of heart disease, and in healthy controls matched for age and sex. Phase analysis revealed abnormal RWM in 19 of 21 diabetic patients. The mean left ventricular global ejection fraction, the mean regional ejection fraction and the mean 1/3 filling fraction were lower and the time to peak ejection, the time to peak filling and the time to peak ejection /cardiac cycle were longer in diabetics than in controls. We found high HbA1c levels in all diabetics. There was no significant difference between patients with and without retinopathy and with and without peripheral neuropathy in terms of left ventricular function and HbA1c levels.

Association between obstructive sleep apnea and persistent-postural perceptual dizziness

2021 ◽  
pp. 1-6
Author(s):  
Anand K. Bery ◽  
Jayson Lee Azzi ◽  
Andre Le ◽  
Naomi S. Spitale ◽  
Judith Leech ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sensitivity And Specificity ◽  
Berlin Questionnaire ◽  
Future Studies ◽  
Obstructive Sleep ◽  
Chronic Dizziness ◽  
Patients At Risk ◽  
The Mean ◽  
The Relationship

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to vestibular dysfunction, but no prior studies have investigated the relationship between Persistent Postural Perceptual Dizziness (PPPD), a common cause of chronic dizziness, and OSA. OBJECTIVE AND METHODS: We determined the frequency of OSA in an uncontrolled group of PPPD patients from a tertiary dizziness clinic based on polysomnogram (PSG). We then assessed the sensitivity and specificity of common OSA questionnaires in this population. RESULTS: Twenty-five patients with PPPD underwent PSG (mean age 47, 60% female, mean BMI 29.5). A majority, or 56%, of patients were diagnosed with OSA, and in most, the OSA was severe. OSA patients were older (56 years versus 40 years, p = 0.0006) and had higher BMI (32 versus 26, p = 0.0078), but there was no clear gender bias (56% versus 64% female, p = 1.00). The mean sensitivity and specificity of the STOP BANG questionnaire for detecting OSA was 86% and 55%, respectively. Sensitivity and specificity of the Berlin Questionnaire was 79% and 45%, respectively. CONCLUSIONS: The prevalence of OSA was much higher in our small PPPD group than in the general population. Screening questionnaires appear to demonstrate good sensitivity to detect PPPD patients at risk of OSA in this small study. Future studies should confirm these findings and determine whether treatment of OSA improves symptoms in PPPD.

ESR and CRP Diagnostic Thresholds for Prosthetic Joint Infection in Hip Hemiarthroplasty

2020 ◽  
Vol 4 (04) ◽  
pp. 187-192
Author(s):  
Jared A. Warren ◽  
Oliver Scotting ◽  
Hiba K. Anis ◽  
James Bircher ◽  
Alison K. Klika ◽  
...  
Keyword(s):  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Musculoskeletal Infection ◽  
Hip Hemiarthroplasty ◽  
Diagnostic Thresholds ◽  
Diagnostic Threshold ◽  
Prosthetic Joint ◽  
The Mean

AbstractDiagnostic thresholds used to standardize the definition for prosthetic joint infection (PJI) have largely focused on total joint arthroplasty (TJA). Established PJI thresholds exist for serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in TJA; however, they do not exist for revision hip hemiarthroplasty (rHHA). The purpose of this study was to establish thresholds for (1) ESR and (2) CRP to diagnose PJI in rHHA. Data were collected on a prospective cohort of 69 rHHA patients undergoing orthopaedic surgery between 1/2017 and 2/2019 in a single health care system. Procedures were categorized as septic or aseptic revisions using Musculoskeletal Infection Society (MSIS) criteria (2013). There were 44 ESRs (n = 28 aseptic, n = 16 septic) and 46 CRPs (n = 29 aseptic, n = 17 septic) available for analysis. Two tailed t-tests were performed to compare the mean ESR and CRP in aseptic and septic cases. Receiver operator characteristic (ROC) curves were generated to obtain diagnostic cutoff thresholds using the Youden's Index (J) for ESR and CRP. The mean ESR was 50.3 ± 30.6 mm/h versus 15.4 ± 17.7 mm/h (p < 0.001), while the mean CRP was 29.9 ± 24.8 mg/L versus 4.1 ± 8.2 mg/L (p < 0.001) for septic and aseptic revisions, respectively. The diagnostic threshold for PJI determined by the ROC curve was 44 mm/h for ESR (sensitivity = 56.3%; specificity = 100.0%; J = 0.563; area under the curve (AUC) = 0.845), while it was 12.5 mg/L for CRP (sensitivity = 70.6%; specificity = 96.6%; J = 0.672; AUC = 0.896). For patients with HHA, an ESR of 44 mm/h was and a CRP of 12.5 mg/L was highly specific for PJI. The thresholds are similar to the MSIS thresholds currently published. Larger prospective trials are needed to establish more robust and conclusive diagnostic criteria for PJI in HHA, including investigations not only of ESR and CRP but synovial white blood cell count and synovial polymorphonuclear leukocytes % as well.

scholarly journals Diurnal Body Temperature and Rate of Passage of Loggers in Lions

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1388
Author(s):  
Ted Friend ◽  
Giulia Corsini ◽  
Vincent Manero ◽  
Raffaella Cocco
Keyword(s):  
Body Temperature ◽  
Time Frame ◽  
Heat Lamp ◽  
Future Studies ◽  
Ambient Temperatures ◽  
Diurnal Patterns ◽  
Data Loggers ◽  
The Mean ◽  
African Lions ◽  
Circadian Patterns

The documentation of diurnal patterns in body temperature in lions could be important because disruption of circadian patterns can be a useful measure of distress. This study quantified changes in body temperature of seven African lions (Panthera leo) at 5 min intervals during cold conditions from noon until the ingested body temperature loggers were expelled the next day. Thirteen loggers were fed to 11 lions during their daily noon feeding, while ambient temperatures were also recorded using six data loggers. The lions had continuous access to their dens and exercise pens during the day but were restricted to their heavily bedded dens that also contained a heat lamp from 23:00 until 08:00 the next day. Body temperatures averaged 37.95 ± 0.42 °C at 15:50, and 36.81 ± 0.17 °C at 06:50 the next day, 30 min before the first loggers passed from a lion, and were significantly different (t-test, t = 8.09, df = 6, p < 0.0003). The mean duration for the time of passage was 22 ± 2.69 (h ± SD), so future studies using the noninvasive feeding of temperature loggers need to consider that time frame.

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 The effects of human leptin fragment(126-140) on pituitary functions in man

2003 ◽  
pp. 407-412 ◽  
Author(s):  
K Hanew
Keyword(s):  
Dose Response ◽  
Area Under The Curve ◽  
Inhibitory Effect ◽  
Pituitary Hormones ◽  
Pituitary Function ◽  
Gh Secretion ◽  
Combined Administration ◽  
The Mean ◽  
Spontaneous Secretion ◽  
Control Study

OBJECTIVE: The effects of human leptin fragment(126-140) on pituitary function in eight healthy, non-obese men were studied. METHODS AND DESIGN: The effects of the fragment on spontaneous secretion of pituitary hormones and endogenous leptin, as well as on GHRH-induced GH secretion were examined. RESULTS: After the administration of the fragment (50 microg i.v. for 150 min), the mean nadir value and 45 min value were significantly lower than that of the control study. Endogenous leptin levels did not decrease significantly following the administration of the leptin fragment. Other pituitary hormones were not affected by the fragment. The area under the curve of the GH response to GHRH(1-44)NH(2) (10 microg, i.v. from 0 to 75 min) was also significantly inhibited by the combined administration of the leptin fragment (100 microg i.v. from -30 to 75 min) (P<0.001). Three subjects were re-examined with larger doses of the leptin fragment (200-400 microg), and even greater GH suppression was observed. CONCLUSIONS: These results indicate that human leptin fragment(126-140) has an inhibitory role in GH secretion, since when administered exogenously this fragment significantly suppressed spontaneous and, in a dose-response manner, GHRH-induced GH secretion. Clear effects of the fragment on other pituitary hormones and an inhibitory effect on endogenous leptin secretion were not observed in this study.

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