scholarly journals Pharmacokinetics of Pentanedioic Acid Imidazolyl Ethanamide in Healthy Volunteers

2021 ◽  
Vol 66 (1-2) ◽  
pp. 19-25
Author(s):  
I. G. Gordeev ◽  
V. I. Kazey ◽  
A. V. Kapashin ◽  
E. Е. Luchinkina ◽  
A. A. Globenko ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Antiviral Agent ◽  
Systemic Circulation ◽  
Medical Intervention ◽  
Intraindividual Variability ◽  
Pharmacokinetic Parameters ◽  
Plasma And Urine Samples ◽  
Long Time ◽  
Pentanedioic Acid

Relevance. Pentanedioic acid imidazolyl ethanamide (PAIE) has been used clinically as an antiviral agent for a long time, however, there is no information in the available literature concerning the dependence of PAIE pharmacokinetics on isoenzymes polymorphism of the cytochrome P450 system (CYP), as well as on the variability of pharmacokinetic parameters in humans. The aim of the study is to determine the main pharmacokinetic parameters of PAIE in healthy volunteers and to assess the contribution of polymorphism of CYP P450 isoenzymes to the variability of pharmacokinetic parameters.Material and methods. The study included 12 healthy volunteers (5 men and 7 women) of the Caucasian race, who took In[1]gavirin® at a dose of 180 mg (2 capsules of 90 mg) on an empty stomach during two dosing periods, separated by a 7-day washout period. Determination of PAIE concentration in blood plasma and urine samples was carried out by high-performance liquid chromatography–mass spectrometry. Polymorphism of CYP genes was analyzed using the polymerase chain re[1]action method in order to analyze the pharmacogenetic features of PAIE metabolism in volunteers during the study.Results. After oral administration, PAIE quickly reached the systemic circulation: the maximum concentration of 578.88±145.21 ng/ml was observed after about 2 hours. Pharmacokinetic parameters of PAIE did not show high intraindividual variability and did not depend on polymorphism of isoenzymes CYP1A1, CYP2C9, and CYP2D6. Within 48 hours after the administration of the studied drug, about half of the taken dose of PAIE was excreted in the urine unchanged, which indicates a significant contribution of the kidneys to the elimination of PAIE. The only adverse event registered in 1 volunteer was a clinically insignificant decrease in the level of leukocytes, which did not require medical intervention and was resolved without consequences.Conclusion. PAIE is characterized by predictable pharmacokinetics, low intraindividual variability of pharmacokinetic parameters, and a favorable safety profile.

scholarly journals Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

2013 ◽  
Vol 58 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Thomas Horvatits ◽  
Reinhard Kitzberger ◽  
Andreas Drolz ◽  
Christian Zauner ◽  
Walter Jäger ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
High Performance ◽  
Area Under The Curve ◽  
Antiviral Agent ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Target Area ◽  
Continuous Venovenous Hemodiafiltration

ABSTRACTGanciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

scholarly journals Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study

Gut ◽  
1998 ◽  
Vol 42 (1) ◽  
pp. 42-46 ◽  
Author(s):  
C P Bearcroft ◽  
D Perrett ◽  
M J G Farthing
Keyword(s):  
Irritable Bowel Syndrome ◽  
Healthy Volunteers ◽  
High Performance ◽  
Area Under The Curve ◽  
Systemic Circulation ◽  
Reversed Phase ◽  
Fluorometric Detection ◽  
Physiological Control ◽  
Creatinine Concentration ◽  
Irritable Bowel

Background—Increased concentrations of 5-hydroxytryptamine (5-HT) can be detected in the systemic circulation after a meal and may be involved in the physiological control of gastrointestinal motility. Abnormalities of 5-HT release after a meal might explain some of the postprandial symptoms associated with the irritable bowel syndrome (IBS).Aim—To investigate the effect of a standard meal on plasma 5-HT and urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations in patients with diarrhoea predominant IBS and in healthy volunteers.Methods—After an overnight fast, six volunteers and five patients with IBS were given a carbohydrate-rich meal. Blood and urine samples were taken before and for four hours after the meal. Platelet-poor plasma 5-HT and urinary 5-HIAA were analysed by reversed phase high performance liquid chromatography with fluorometric detection. 5-HIAA was expressed as a ratio with urinary creatinine concentration, which was measured by spectrophotometry.Results—During the four hour postprandial period, 5-HT concentrations were significantly higher in patients with IBS than in healthy volunteers at 0.5 hours (p<0.05), 2 hours (p<0.05) and 2.5 hours (p<0.05). 5-HT was not detected in the plasma in the fasting state in patients or volunteers. Median peak 5-HT in patients with IBS (359 (198–796) nmol/l) was significantly greater than volunteers (83 (7–190)) (p<0.05). “Area under the curve” for 5-HT detection was greater for patients with IBS (317 (138–771)) than for healthy volunteers (51 (4–129); p<0.05).The duration of the 5-HT peak was significantly longer in patients with IBS (3 (1–3) hours) than in the healthy volunteers (1 (1–1) hours; p<0.01). Postprandial urinary median 5-HIAA values in controls (5.6 (5.5–5.8) μmol/mmol creatinine) and patients with IBS (3.0 (2.5–6.8) μmol/mmol creatinine) were not significantly different from preprandial values (controls: 5.9 (5.5–6.6) μmol/mmol creatinine; patients with IBS: (6.2 (2.4–9.3) μmol/mmol creatinine).Conclusion—These findings indicate that there may be a difference in the way that 5-HT is released in patients with diarrhoea predominant IBS, and could suggest a possible role for 5-HT in the postprandial symptoms of these patients.

scholarly journals Dissolution efficiency and bioequivalence study using urine data from healthy volunteers: a comparison between two tablet formulations of cephalexin

2015 ◽  
Vol 51 (2) ◽  
pp. 383-392
Author(s):  
Cristina Helena dos Reis Serra ◽  
Kyung Hee Chang ◽  
Thaisa Marinho Dezani ◽  
Valentina Porta ◽  
Sílvia Storpirtis
Keyword(s):  
Urinary Excretion ◽  
Healthy Volunteers ◽  
High Performance ◽  
Bioequivalence Study ◽  
Immediate Release ◽  
International Standards ◽  
Pharmacokinetic Parameters ◽  
Tablet Formulations ◽  
Dissolution Efficiency

<p>The aim of the present study was to assess the bioequivalence of two cephalexin tablet formulations available in the Brazilian market (product A as reference formulation and product B as test formulation). Dissolution efficiency (DE%) was calculated for both formulations to evaluate their <italic>in vitro</italic>biopharmaceutical features. The oral bioequivalence study was performed in twenty-four healthy volunteers in a crossover design. Single oral dose (tablet containing 500 mg of cephalexin) of each product was administered with two weeks of washout period. Urinary concentrations of cephalexin were measured by high-performance liquid chromatography (HPLC) method and pharmacokinetics parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of cephalexin excreted in the urine, the total amount of cephalexin excreted in the urine and the maximum urinary excretion rate of cephalexin. DE values of immediate-release cephalexin tablets (500 mg) were 68.69±4.18% for product A and 71.03±6.63% for product B. Regarding the dissolution test of the two brands (A and B) analysed, both were in compliance with the official pharmacopeial specifications, since the dissolution of both formulations was superior to 80% of the amount declared in the label after 45 minutes of test (A=92.09%±1.84; B=92.84%±1.08). The results obtained indicated that the products A and B are pharmaceutical equivalents. Confidence intervals for the pharmacokinetic parameters were in compliance with the international standards, indicating that products A and B can be considered bioequivalents and, therefore, interchangeable.</p>

scholarly journals Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

2013 ◽  
Vol 49 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Xi-Qing Yan ◽  
Zhi-Gang Chen ◽  
Rong-Liang Wang ◽  
Jun Yang ◽  
Fang Ai ◽  
...  
Keyword(s):  
Controlled Release ◽  
Oral Dose ◽  
Sustained Release ◽  
Healthy Volunteers ◽  
Single Oral Dose ◽  
High Performance ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Diltiazem Hydrochloride ◽  
New Formulation

The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.

Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors.

1995 ◽  
Vol 13 (11) ◽  
pp. 2835-2841 ◽  
Author(s):  
S Kaul ◽  
L N Igwemezie ◽  
D J Stewart ◽  
S Z Fields ◽  
M Kosty ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Performance ◽  
Plasma Concentrations ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Etoposide Phosphate ◽  
Elimination Half ◽  
Constant Rate

PURPOSE To assess the pharmacokinetics and bioequivalence of etoposide following intravenous (i.v.) administration of etoposide phosphate (Etopophos; Bristol-Myers Squibb, Princeton, NJ), a prodrug of etoposide, and VePesid (Bristol-Myers Squibb). PATIENTS AND METHODS Forty-nine solid tumor patients were randomized to receive Etopophos or VePesid on day 1 of a day-1,3,5 schedule of treatment. The alternate drug was given on day 3 and repeated on day 5. The dose, 150 mg/m2 of etoposide equivalent, was administered by constant rate infusion over 3.5 hours. The plasma concentrations of etoposide phosphate and etoposide were determined using validated high-performance liquid chromatography (HPLC) assays. Pharmacokinetic parameters were calculated by a noncompartmental method. Etopophos was considered to be bioequivalent to VePesid if the 90% confidence limits for the differences in mean maximum concentration (Cmax) and AUCinf of etoposide were contained within 80% to 125% for the long-transformed data. RESULTS Forty-one patients were assessable for pharmacokinetics and bioequivalence assessment. Following i.v. administration, etoposide phosphate was rapidly and extensively converted to etoposide in systemic circulation, resulting in insufficient data to estimate its pharmacokinetics. The mean bioavailability of etoposide from Etopophos, relative to VePesid, was 103% (90% confidence interval, 99% to 106%) based on Cmax, and 107% (90 confidence interval, 105% to 110%) based on area under the concentration versus time curve from zero to infinity (AUCinf) values. Mean terminal elimination half-life (t1/2), steady-state volume of distribution (Vss), and total systemic clearance (CL) values of etoposide were approximately 7 hours, 7 L/m2, and 17 mL/min/m2 after Etopophos and VePesid treatments, respectively. The main toxicity observed was myelosuppression, characterized by leukopenia and neutropenia. CONCLUSION With respect to plasma levels of etoposide, i.v. Etopophos is bioequivalent to i.v. VePesid.

scholarly journals Pharmacokinetic parameters of Amoxicillin in Bangladeshi volunteers: a preliminary evaluation

2014 ◽  
Vol 26 (1-2) ◽  
pp. 1-9
Author(s):  
Reefat Zaman Chowdhury ◽  
Md. Saiful Islam ◽  
Md. Sayedur Rahman
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Oral Route ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
Preliminary Evaluation ◽  
The Difference ◽  
Bangladeshi Population

The present study was designed to get preliminary idea about the pharmacokinetic behavior of the Bangladeshi population through estimating plasma amoxicillin concentration by High-Performance Liquid Chromatography (HPLC) with ultraviolet detection. In this study, Bangladeshi healthy volunteers were divided in two groups, 8 Bangladeshi Bangalee and 7 Bangladeshi Tribal male healthy volunteers. Both the groups received 500 mg of amoxicillin in oral route and blood samples were collected at 0, 30, 60, 120, 180, 360 and 480 minutes after drug administration. After 1 week of washout period, same volunteers of two groups received 500 mg of amoxicillin in intravenous route. In case of oral route, the Cmax, AUC0–8h, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 6.78 ± 1.20 & 9.10 ± 1.34 ìg/mL, 1290.13 ± 158.39 & 1766.06 ± 188.37 ìg min/mL, 82.50 ± 32.05 & 102.86 ± 29.28 min and 96.05 ± 3.80 & 88.15 ± 5.33 min respectively. The difference in Cmax, AUC0–8h and T1/2 values between these two groups of volunteers was significant (p<0.01, p<0.001 and p<0.01 respectively). However, the difference in Tmax was not significant (p>0.05). In case of intravenous route, the C30 min and AUC0–8h values for Bangladeshi Bangalee and Tribal healthy volunteers were 17.88 ± 1.14 & 18.58 ± 0.71 ìg/mL, 2297.96 ± 222.49 & 2376.41 ± 149.99 ìg min/mL respectively and the difference was not significant (p>0.05). The T1/2 for Bangladeshi Bangalee and Tribal healthy volunteers were 97.50 ± 3.33 & 94.40 ± 2.33 min respectively and the difference was significant (p<0.05). The Mean Percent Absolute Bioavailability in Bangladeshi Bangalee and Tribal healthy volunteers was 56.76 ± 5.39 and 74.17 ± 3.90 respectively and the difference was highly significant (p<0.001). The study concluded that the pharmacokinetic parameters of amoxicillin significantly varied among Bangladeshi Bangalee and Bangladeshi Tribal healthy volunteers indicating necessity of further study on population pharmacokinetic to formulate tailor-made drug therapy in these groups of people. http://dx.doi.org/10.3329/bjpp.v26i1-2.19958 Bangladesh J Physiol Pharmacol 2010; 26(1&2) : 1-9

Revealing changes in curcumin bioavailability using vitamin C as an enhancer by HPLC-MS/MS

2019 ◽  
Vol 16 ◽  
Author(s):  
Xufen Dai ◽  
Jiaxue Hao ◽  
Ying Feng ◽  
Jing Wang ◽  
Qiannan Li ◽  
...  
Keyword(s):  
Vitamin C ◽  
High Performance ◽  
Internal Standard ◽  
Fold Increase ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Solution Ph ◽  
Esi Ms ◽  
Simple Strategy ◽  
Isolated Compound

Background: Curcumin (CUR), a natural isolated compound from turmeric, has been the promising star in fighting many diseases but the broad application of curcumin has been limited ascribed to low bioavailability. Objective: The aim of this study is to pursue the enhancement of curcumin bioavailability through co-administration of vitamin C. Methods: Such purpose was achieved through the analysis of curcumin pharmacokinetics by high performance liquid chromatography coupled with electrospray ionization - tandem mass spectrometry (HPLC - ESI - MS/MS). The plasma was separated on a C18 reverse phase column using acetonitrile and ammonium formate solution (pH 6.5; 2.0 mM) at 0.8 mL/min. MS/MS detection was carried out in negative mode using mass patterns of m/z 367.0 > 216.7 for curcumin and m/z 265.2 > 223.9 for internal standard (honokiol). Results: Successful application of the proposed method in the pharmacokinetic study presented clear changes in key pharmacokinetic parameters including the growth of AUC (0-t) up to 2.4 times, 2.2-fold increase of Cmax, 2.2-fold loss of CL, and 1.5-fold diminishment of t1/2. Conclusion: We developed an HPLC-ESI-MS/MS method for determination of curcumin in rat plasma and validated the improvement of bioavailability of curcumin through co-administration of vitamin C. We reasoned these changes to the inhibition of lipid peroxidation induced by the use of vitamin C. Such a simple strategy is possible to become an alternative for enhancing curcumin efficiency in practice.

scholarly journals Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers

2011 ◽  
Vol 55 (6) ◽  
pp. 2927-2936 ◽  
Author(s):  
J. B. Bulitta ◽  
M. Kinzig ◽  
C. B. Landersdorfer ◽  
U. Holzgrabe ◽  
U. Stephan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Volunteers ◽  
High Performance ◽  
Standard Dose ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Nonparametric Bootstrap ◽  
Population Pk ◽  
Total Body ◽  
Similar Body

ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (P≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.

Sign in / Sign up

Export Citation Format

Share Document