Effect of Flying at High Altitude on Early Exposure of Paracetamol in Humans

Drug Research ◽  
2018 ◽  
Vol 69 (06) ◽  
pp. 348-351
Author(s):  
Nasir Idkaidek ◽  
Ahmad Al-Ghazawi
Keyword(s):  
High Altitude ◽  
Liver Blood Flow ◽  
Compartmental Analysis ◽  
Therapeutic Index ◽  
Similar Rate ◽  
Pharmacokinetic Parameters ◽  
Early Exposure ◽  
Healthy Human ◽  
Saliva Concentration ◽  
Rate Of Absorption

AbstractPharmacokinetics of paracetamol (APAP) was studied on-board during an air flight and compared to those on ground after 500 mg oral dose in 20 healthy human volunteer in parallel design study. Saliva samples were obtained every 15 min up to 2 h after dosing. Pharmacokinetic parameters were calculated by non compartmental analysis and one compartment models using Winnonlin program V5.2. Results have showed that on-board to ground ratios for area under curves AUC0→1, AUC0→2, time to reach maximum saliva concentration Tmax, absorption rate constant Ka and maximum saliva concentration Cmax were 0.62, 0.38, 1.01, 0.81 and 0.79 respectively. Effective membrane permeability coefficients were optimized by Nelder-Mead algorithm using Simcyp program V13. This showed similar rate of absorption and early exposure up to one hour, and lower bioavailability after 1 h on-board. This can be explained by the increased liver blood flow at high altitude that led to increased liver metabolism on-board. However, APAP elimination parameters were not calculated due to short sampling time. This suggests a need for dose adjustment on-board during long air flights, especially for narrow therapeutic index drugs with flow limited metabolism.

scholarly journals The pharmacokinetics of acyl, des-acyl, and total ghrelin in healthy human subjects

2013 ◽  
Vol 168 (6) ◽  
pp. 821-828 ◽  
Author(s):  
Jenny Tong ◽  
Nimita Dave ◽  
Ganesh M Mugundu ◽  
Harold W Davis ◽  
Bruce D Gaylinn ◽  
...  
Keyword(s):  
Human Subjects ◽  
Dose Range ◽  
Area Under The Curve ◽  
Compartmental Analysis ◽  
Volume Of Distribution ◽  
Metabolic Effects ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Gh Secretion ◽  
Total Ghrelin

BackgroundGhrelin stimulates GH secretion and regulates energy and glucose metabolism. The two circulating isoforms, acyl (AG) and des-acyl (DAG) ghrelin, have distinct metabolic effects and are under active investigation for their therapeutic potentials. However, there is only limited data on the pharmacokinetics of AG and DAG.ObjectivesTo evaluate key pharmacokinetic parameters of AG, DAG, and total ghrelin in healthy men and women.MethodsIn study 1, AG (1, 3, and 5 μg/kg per h) was infused over 65 min in 12 healthy (8 F/4 M) subjects in randomized order. In study 2, AG (1 μg/kg per h), DAG (4 μg/kg per h), or both were infused over 210 min in ten healthy individuals (5 F/5 M). Plasma AG and DAG were measured using specific two-site ELISAs (study 1 and 2), and total ghrelin with a commercial RIA (study 1). Pharmacokinetic parameters were estimated by non-compartmental analysis.ResultsAfter the 1, 3, and 5 μg/kg per h doses of AG, there was a dose-dependent increase in the maximum concentration (Cmax) and area under the curve (AUC(0–last)) of AG and total ghrelin. Among the different AG doses, there was no difference in the elimination half-life, systemic clearance (CL), and volume of distribution. DAG had decreased CL relative to AG. The plasma DAG:AG ratio was ∼2:1 during steady-state infusion of AG. Infusion of AG caused an increase in DAG, but DAG administration did not change plasma AG. Ghrelin administration did not affect plasma acylase activity.ConclusionsThe pharmacokinetics of AG and total ghrelin appears to be linear and proportional in the dose range tested. AG and DAG have very distinct metabolic fates in the circulation. There is deacylation of AG in the plasma but no evidence of acylation.

scholarly journals Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

Rectal Administration of Ibuprofen: Comparison of Enema and Suppository Form

Drug Research ◽  
2021 ◽  
Author(s):  
Budi Prasaja ◽  
Yahdiana Harahap ◽  
Monika Sandra ◽  
Irene Iskandar ◽  
Windy Lusthom ◽  
...  
Keyword(s):  
Phase 1 ◽  
Rectal Administration ◽  
Pharmacokinetic Parameters ◽  
P Value ◽  
Open Label ◽  
Post Dose ◽  
Anova Model ◽  
Equal Dose ◽  
Rate Of Absorption ◽  
The Mean

AbstractIbuprofen is a widely used and well-tolerated analgesic and antipyretic. It is desirable to have a formulation with a rapid rate of absorption because it is required for rapid pain relief and temperature reduction. Previous studies have described the pharmacokinetic profiles of ibuprofen suppository and the mean peak times of ibuprofen suppository were around 1.8 hours, indicating a slower rate of absorption. The aim of this study is to compare the pharmacokinetic parameters of rectal administration of ibuprofen between enema and suppository form in order to provide evidence for the faster absorption rates of ibuprofen enema. This study was a phase-1 clinical study, open-label, randomized and two-way crossover with one-week washout period comparing the absorption profile of equal dose of ibuprofen administered rectally in two treatment phases: ibuprofen suppository and enema. Blood samples were collected post dose for pharmacokinetic analyses. Tmax was analyzed using a Wilcoxon matched paired test. A standard ANOVA model, appropriate for bioequivalence studies was used and ratios of 90% confidence intervals were calculated. This study showed that Tmax for ibuprofen enema was less than half that of ibuprofen suppository (median 40 min vs. 90 min, respectively; p-value=0.0003). Cmax and AUC0–12 for ibuprofen enema were bioequivalent to ibuprofen suppository, as the ratio of test/reference=104.52%, 90% CI 93.41–116.95% and the ratio of test/reference=98.12%, 90%CI 93.34–103.16%, respectively, which fell within 80–125% bioequivalence limit. The overall extent of absorption was similar to the both, which were all well tolerated. In terms of Tmax, Ibuprofen enema was absorbed twice as quickly as from ibuprofen suppository. Therefore it is expected that an ibuprofen enema may provide faster onset of analgesic and antipyretic benefit.

Pharmacokinetics and bioequivalence of generic etoricoxib in healthy volunteers

2021 ◽  
Vol 10 (3) ◽  
pp. 113-118
Author(s):  
Nishalini Harikrishnan ◽  
Ka-Liong Tan ◽  
Kar Ming Yee ◽  
Alia Shaari Ahmad Shukri ◽  
Nalla Ramana Reddy ◽  
...  
Keyword(s):  
Compartmental Analysis ◽  
Bioequivalence Study ◽  
Active Pharmaceutical Ingredient ◽  
Pharmacokinetic Profile ◽  
Time Profile ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Reference Drug ◽  
Test Formulation ◽  
R Ratio

Introduction/Study Objectives: A bioequivalence study was performed to compare the pharmacological profile of innovator etoricoxib (ETO) with a newly developed generic ETO, both in a 120 mg tablet formulation. A dissolution study was conducted to optimize the formulation process before evaluating physical changes in the active pharmaceutical ingredient and the formulated product. Methods: This was a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover, truncated bioequivalence study involving a washout period of ten days. A total of 26 healthy male volunteers were recruited. The pharmacokinetic profile of the test formulation was compared with the reference formulation. Results/Discussion: The pharmacokinetic parameters of ETO were calculated based on the plasma drug concentration-time profile using non-compartmental analysis to determine its safety profile and tolerability. The Test/Reference (T/R) ratio of ETO was 104.36% (90% confidence interval (CI): 98.30%–110.80%) for area under curve (AUC)0-72 while the T/R ratio of maximum concentration (Cmax) was 101.39% (92.15%–111.56%). The 90% CI of the Cmax and AUC0-72 of ETO were within acceptable bioequivalence limits of 80%–125%. All values were within the predetermined limits of the Association of Southeast Asian Nation (ASEAN) bioequivalence guidelines. Conclusion: The test formulation was found to be bioequivalent with respect to the reference drug, according to ASEAN bioequivalence guidelines.

scholarly journals Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Paula Almodóvar ◽  
David Briskey ◽  
Amanda Rao ◽  
Marín Prodanov ◽  
Antonio M. Inarejos-García
Keyword(s):  
Research Work ◽  
Crocus Sativus ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Digestion Process ◽  
Oral Consumption ◽  
Quantification Analysis ◽  
Saffron Extract ◽  
Galenic Form

There are few studies about the pharmacokinetics of the low-molecular mass carotenoids crocetin or crocin isomers from saffron (Crocus sativus L.). None has been performed with a galenic preparation of a standardised saffron extract. The aim of the present research work was to study the effect of in vitro digestion process on the main bioactive components of saffron extract tablets and the corresponding pharmacokinetic parameters in humans. Pharmacokinetics were calculated collecting blood samples every 30 min during the first 3 h and at 24 h after administration of two different concentrations (56 and 84 mg of the saffron extract) to 13 healthy human volunteers. Additionally, an in vitro digestion process was performed in order to determine the bioaccessibility of saffron main bioactive compounds. Identification and quantification analysis were performed by HPLC-PAD/MS. Digestion resulted in 40% of bioaccesibility for crocin isomers, whereas, safranal content followed an opposite trend increasing about 2 folds its initial concentration after the digestion process. Crocetin in plasma was detected in a maximum concentration (Cmax) in blood between 60 and 90 min after oral consumption with dose-dependent response kinetics, showing that crocin isomers from galenic preparation of saffron extract are rapidly transformed into crocetin. The results showed that this tested galenic form is an efficient way to administer a saffron extract, since the observed crocetin Cmax was similar and more quickly bioavailable than those obtained by other studies with much higher concentrations of crocetin.

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

Myoglobin content and enzymatic activity of muscle and altitude adaptation

1962 ◽  
Vol 17 (2) ◽  
pp. 301-305 ◽  
Author(s):  
Baltazar Reynafarje
Keyword(s):  
Cytochrome C ◽  
Enzymatic Activity ◽  
High Altitude ◽  
Sea Level ◽  
Human Subjects ◽  
Reduced Form ◽  
Sartorius Muscle ◽  
Healthy Human ◽  
Altitude Adaptation ◽  
Made In

Quantitative determinations of myoglobin were made in the sartorius muscle of healthy human subjects native to sea level and high altitude. The specific activities of the reduced form of diphosphopyridine nucleotide oxidase (DPNH-oxidase), DPNH- and the reduced form of triphosphopyridine nucleotide (TPNH)-cytochrome c reductases, transhydrogenase, and isocitric and lactic dehydrogenases were also examined. There was found a significantly higher myoglobin concentration in the muscle of the high-altitude native as compared with the sea-level resident. The enzyme systems DPNH-oxidase, TPNH-cytochrome c reductase, and transhydrogenase similarly showed a significantly higher activity in the altitude resident. It was concluded that the respiratory capacity of the muscle was apparently higher in the altitude native than in the sea-level one. The enhanced enzymatic activity was probably related to the higher pigment content of the skeletal muscle. Results on myoglobin determinations in several other muscles from certain sea-level patients are discussed. Submitted on July 24, 1961

scholarly journals Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seonghae Yoon ◽  
Seongmee Jeong ◽  
Eben Jung ◽  
Ki Soon Kim ◽  
Inseung Jeon ◽  
...  
Keyword(s):  
Adverse Event ◽  
Plasma Concentration ◽  
Compartmental Analysis ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Digit Symbol Substitution Test ◽  
Cyp3a4 Activity ◽  
Post Dose ◽  
Time Curve ◽  
Apparent Clearance

AbstractTo investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration–time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.

scholarly journals Influence of Altitude on Pulmonary Function A Comparative Study on Indian and Kyrgyz Healthy Males

2020 ◽  
Vol 5 (1) ◽  
pp. 3-9
Author(s):  
Priya Gaur ◽  
Supriya Saini ◽  
Koushik Ray ◽  
Almazbek Akunov ◽  
Abdirashit Maripov ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Function ◽  
High Altitude ◽  
Ethnic Origin ◽  
Moderate Increase ◽  
Small Airways ◽  
Healthy Human ◽  
Maximum Increase ◽  
Altitude Exposure ◽  
Human Male

Variation in lung function at high altitude (HA) impacts the working capacity of individuals and may predispose body towards hypoxia induced illness. So, we investigated the changes in pulmonary function of healthy human male volunteers belonging to two different ethnicities i.e. Indian and Kyrgyz. Twenty, age and BMI matched, volunteers (Indian=10 and Kyrgyz=10) were recruited for the study. Measurement for pulmonary functions (FVC, FEV1, FEV1/FVC ratio, PEF, FEF 25-75%, MEF 25%, MEF 50%, MEF 75%, MVV) were performed on each individual at basal (800 m) and high altitude (4,111 m) on day 3,7,14 and 21. Results indicate that Kyrgyz has comparatively higher FVC, FEV1, PEF and MVV values and lower FEV1/FVC ratio upon altitude induction than those of Indian counterparts. Mid expiratory flow FEF25-75% was significantly increased in Kyrgyz upon altitude induction indicate more proficient lung emptying while only moderate increase at day 7 in Indian. MEF25% was significantly increased in Kyrgyz, while no change is observed in Indians at high altitude which indicates that 75% of lung emptying through small airways is better in Kyrgyz. MEF 50% and MEF 75% increased with altitude in both groups. For MVV, the maximum increase was ~17% in Indian at HA14 (p<0.01) and in Kyrgyz ~33% (p<0.001) at HA14 as compared to basal. Difference in lung function response observed, indicates that Kyrgyz has better pulmonary dynamics during altitude exposure as compared to Indian counterparts. The varied result observed may be due to different ethnic origin of the groups.

scholarly journals Effect of Co-Medication on the Pharmacokinetic Parameters of Phenobarbital in Asphyxiated Newborns

2015 ◽  
pp. S513-S519 ◽  
Author(s):  
M. ŠÍMA ◽  
P. POKORNÁ ◽  
K. HRONOVÁ ◽  
O. SLANAŘ
Keyword(s):  
Area Under The Curve ◽  
Compartmental Analysis ◽  
Volume Of Distribution ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacokinetic Parameters ◽  
Vasoactive Medication ◽  
Inotropic Score ◽  
Study Population ◽  
Vasoactive Inotropic Score ◽  
Ischemic Encephalopathy

Phenobarbital is an anticonvulsive drug widely used in newborns with hypoxic-ischemic encephalopathy. The objective of our study was to describe possible effect of frequently co-administered medications (dopamine, dobutamine, norepinephrine, furosemide, phenytoin, and analgesics) on the phenobarbital pharmacokinetics in full term newborns with hypoxic-ischemic encephalopathy. Phenobarbital pharmacokinetic parameters (standardized intravenous loading dose was 10-20 mg/kg, maintenance dose 2-6 mg/kg/day) were computed using non-compartmental analysis. Co-medication was evaluated throughout the whole treatment period up to 5 days. Volume of distribution, clearance, and half-life median values (95 % CI) for phenobarbital in the whole study population (n=37) were 0.48 (0.41-0.56) l/kg, 0.0034 (0.0028-0.0040) l/h/kg, and 93.7 (88.1-99.2) h, respectively. Phenobarbital pharmacokinetic parameters were not significantly affected by vasoactive drugs (dopamine, dobutamine, and norepinephrine), furosemide, phenytoin, or analgesics. Furthermore, no dose-dependent alteration of phenobarbital pharmacokinetic parameters was noted for vasoactive medication at doses equivalent to cumulative vasoactive-inotropic score (area under the curve in a plot of vasoactive-inotropic score against time) 143.2-8473.6, furosemide at cumulative doses of 0.2-42.9 mg/kg, or phenytoin at cumulative doses of 10.3-46.2 mg/kg. Phenobarbital pharmacokinetics was not affected by investigated co-administered drugs used in newborns with hypoxic-ischemic encephalopathy in real clinical settings.

Sign in / Sign up

Export Citation Format

Share Document