Stereospecific disposition of fluvastatin in streptozotocin-induced diabetic rats

2002 ◽  
Vol 80 (11) ◽  
pp. 1071-1075 ◽  
Author(s):  
Adriana Rocha ◽  
Eduardo Barbosa Coelho ◽  
Vera Lucia Lanchote
Keyword(s):  
Plasma Concentration ◽  
Streptozotocin Diabetes ◽  
Diabetic Rats ◽  
Racemic Mixture ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Chiral Hplc ◽  
Time Curve ◽  
Stereoselective Pharmacokinetics ◽  
Streptozotocin Induced Diabetes

The study reports on the stereoselective pharmacokinetics of fluvastatin, a racemic mixture of (–)-(3S,5R)- and (+)-(3R,5S)-enantiomers, in streptozotocin-induced diabetic rats. Wistar (control) and streptozotocin-induced diabetic rats (n = 6/time point) received by oral gavage racemic fluvastatin (5 mg/kg), and blood samples were collected until 24 h. The enantiomers were analysed by chiral HPLC with fluorescence detection. The pharmacokinetic parameters were analysed by Wilcoxon and Mann–Whitney tests. The results are reported as means (95% CI). The following differences (p < 0.05) were observed between the control and diabetic groups, respectively: maximum plasma concentration (Cmax) of (–)-(3S,5R), 410.0 (310.0–510.0) versus 532.6 (463.5–601.8) ng·mL–1; area under the plasma concentration versus time curve (AUC0–[Formula: see text]) for (–)-(3S,5R), 4342.4 (3775.7–4909.0) versus 3025.2 (2218.9–3831.5) ng·h·mL–1; apparent total clearance (Cl/f) of (–)-(3S,5R), 0.6 (0.5–0.7) versus 0.9 (0.6–1.1) L·h–1·kg–1; AUC0–[Formula: see text] for (+)-(3R,5S), 493.5 (376.9–610.1) versus 758.5 (537.1–980.0) ng·h·mL–1; and Cl/f of (+)-(3R,5S), 5.3 (3.9–6.8) versus 3.5 (2.6-4.4) L·h–1·kg–1. Streptozotocin-induced diabetes in rats alters the pharmacokinetics of fluvastatin in a stereoselective manner. Key words: fluvastatin, enantiomers, pharmacokinetics, rats, streptozotocin diabetes.

scholarly journals L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Laura Vacca ◽  
Paola Grassini ◽  
Stephen Pawsey ◽  
Holly Whale ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Concentration ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Double Blind ◽  
Time Curve ◽  
Randomised Study ◽  
Effervescent Tablet

Objectives.To characterize the pharmacokinetic profile of levodopa (L-dopa) and carbidopa after repeated doses of the effervescent tablet of melevodopa/carbidopa (V1512; Sirio) compared with standard-release L-dopa/carbidopa in patients with fluctuating Parkinson’s disease. Few studies assessed the pharmacokinetics of carbidopa to date.Methods.This was a single-centre, randomized, double-blind, double-dummy, two-period crossover study. Patients received V1512 (melevodopa 100 mg/carbidopa 25 mg) or L-dopa 100 mg/carbidopa 25 mg, 7 doses over 24 hours (Cohort 1), 4 doses over 12 hours (Cohort 2), or 2 doses over 12 hours in combination with entacapone 200 mg (Cohort 3). Pharmacokinetic parameters included area under the plasma-concentration time curve (AUC), maximum plasma concentration (Cmax), and time toCmax(tmax).Results.Twenty-five patients received at least one dose of study medication. L-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after V1512 versus L-dopa/carbidopa, both over time and between patients. Accumulation of L-dopa in plasma was less noticeable with V1512. Carbidopa exposure and interpatient variability was lower when V1512 or L-dopa/carbidopa was given in combination with entacapone. Both treatments were well tolerated.Conclusions.V1512 provides a more reliable L-dopa pharmacokinetic profile versus standard-release L-dopa/carbidopa, with less drug accumulation and less variability. This trial is registered with ClinicalTrials.govNCT00491998.

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 Pharmacokinetics of Itraconazole in Diabetic Rats

2009 ◽  
Vol 54 (2) ◽  
pp. 931-933 ◽  
Author(s):  
Unji Lee ◽  
Young H. Choi ◽  
So H. Kim ◽  
Byung K. Lee
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Concentration ◽  
Oral Administration ◽  
Intrinsic Clearance ◽  
Diabetic Rats ◽  
Clearance Rates ◽  
Time Curve ◽  
Concentration Time ◽  
Streptozotocin Induced Diabetes ◽  
Plasma Concentration Time Curve

ABSTRACT After intravenous or oral administration of 10 mg/kg itraconazole to rats with streptozotocin-induced diabetes mellitus and to control rats, the total area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24) for itraconazole and that for its metabolite, 7-hydroxyitraconazole, were similar between the two groups of rats. This may be explained by the comparable hepatic and intestinal intrinsic clearance rates for the disappearance of itraconazole and the formation of 7-hydroxyitraconazole in both groups of rats.

scholarly journals Effect of lopinavir and efavirenz on pharmacokinetics and pharmacodynamics of glibenclamide in diabetic rats

2017 ◽  
Vol 4 (6) ◽  
pp. 245
Author(s):  
Prashanth Vennapanja ◽  
Ajmera Ramarao
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Severe Hypoglycemia ◽  
Diabetic Rats ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Elimination Half ◽  
Antiretroviral Drug ◽  
The Impact

Objective: The aim of the study is whether the impact of Efavirenz and Lopinavir will increase the plasma level of Glibenclamide or not. Efavirenz and Lopinavir is an antiretroviral drug to treat HIV AIDS and inhibits cytochrome P450-3A4. Multiple CYP isoforms are involved in the metabolism of Glibenclamide like CYP2C8 and CYP3A4. Hence there is more possibility of Efavirenz and Lopinavir to inhibit the metabolism of Glibenclamide by inhibiting CYP 3A4.Methods: Efavirenz and Lopinavir (10 mg/kg,p.o.) alone and along with Glibenclamide (10 mg/kg, p.o.) was given to normal and diabetic rats. PK/PD parameters were studied. In the rats co-treated with Efavirenz and Lopinavir and Glibenclamide.Results: The pharmacokinetic parameters like clearance of Glibenclamide was reduced, peak plasma concentration, area under the plasma concentration time curve and elimination half-life were significantly increased when compared to pioglitazone treated rats.Conclusions: This study revealed that lopinavir and efavirenz affected the disposition of Glibenclamide in rats probably by the inhibition of CYP3A4, leading to increasing Glibenclamide concentrations that could increase the efficacy of Glibenclamide or it may causes severe hypoglycemia. Therefore, its warrants to use relatively less dose of Glibenclamide than the normal dose.

Comparative Human Bioavailability Study of Macrocrystalline Nitrofurantoin and Two Prolonged-Action Hydroxymethylnitrofurantoin Preparations

1988 ◽  
Vol 22 (12) ◽  
pp. 959-964 ◽  
Author(s):  
Pieter J.M. Guelen ◽  
Johannes B.J. Boerema ◽  
Tom B. Vree
Keyword(s):  
Plasma Concentration ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Prolonged Action ◽  
Time Curve ◽  
Significant Difference ◽  
Bioavailability Study ◽  
Total Body ◽  
Single Blind ◽  
Healthy Females

This single-blind crossover study compared the human bioavailability of macrocrystalline nitrofurantoin (Furadantine MC) and two prolonged-action hydroxymethylnitrofurantoin formulations (Urfadyn PL, bid, and Uridurine, tid), based on plasma nitrofurantoin concentrations and urinary nitrofurantoin excretion. The drugs were administered to 16 healthy females for a single day according to the recommended daily dosages. For comparison, Furadantine MC was administered both at the qid dosage recommended by the manufacturer and at tid dosage. Pharmacokinetic parameters determined were maximum plasma concentration after first dose, minimum plasma concentration after first dose, area under the plasma concentration-time curve (AUC), cumulative renal excretion over 30 hours (ARE), overall renal clearance, total body clearance, and bioavailability relative to Furadantine MC qid, based on plasma AUC (F) and ARE (Fren). F for Furadantine MC 100 mg tid was 108 ± 25 percent (mean ± SD); for Uridurine 100 mg tid and Urfadyn PL 100 mg bid, F equalled 86 ± 33 percent and 53 ± 20 percent (p<0.05), respectively. A similar relationship was observed between Fren for Furadantine MC 100 mg qid and the respective Fren of Furadantine MC 100 mg tid, Uridurine 100 mg tid, and Urfadyn PL 100 mg bid. No significant difference was found between the respective F and Fren of each of the drugs studied. Although bioavailability was comparable for Furadantine MC tid and qid, the single-day design of these studies precludes inferring that these dosage schedules are therapeutically equivalent. However, the significantly lower relative bioavailabilities for the prolonged-action hydroxymethylnitrofurantoin formulations suggest that Urfadyn PL 100 mg bid and Uridurine 100 mg tid are not pharmacokinetically equivalent to Furadantine MC.

scholarly journals Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Eric Wenzler ◽  
Kristen L. Bunnell ◽  
Susan C. Bleasdale ◽  
Scott Benken ◽  
Larry H. Danziger ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Critically Ill ◽  
Critically Ill Patient ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Continuous Venovenous Hemofiltration ◽  
Total Clearance ◽  
Time Curve ◽  
Drug Concentrations

ABSTRACT Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were as follows: maximum plasma concentration (C max), 61.10 and 14.54 mg/liter; minimum plasma concentration (C min), 31.96 and 8.45 mg/liter; half-life (t 1/2), 6.07 and 6.78 h; apparent volume of distribution at the steady state (V ss), 27.23 and 30.81 liters; total clearance at the steady state (CLss), 2.87 and 2.95 liters/h; area under the concentration-time curve from 0 to 8 h (AUC0–8), 347.87 and 85.69 mg · h/liter. Concentrations of ceftazidime in plasma exceeded the ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%, respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for avibactam was 1.59 liters/h, representing 57.1% of the total clearance of ceftazidime and 54.3% of the total clearance of avibactam. Further data that include multiple patients and dialysis modes are needed to verify the optimal ceftazidime-avibactam dosing strategy during critical illness and CVVH.

Comparative Bioavailability and Safety of Two Intramuscular Ceftriaxone Formulations

1996 ◽  
Vol 30 (11) ◽  
pp. 1223-1226 ◽  
Author(s):  
Encarnación C Suárez ◽  
Jana R Grippi
Keyword(s):  
Plasma Concentration ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Double Blind ◽  
Time Curve ◽  
Mean Values ◽  
Concentration Time ◽  
Clinical Research Center ◽  
Comparative Bioavailability ◽  
Concentrated Solution

OBJECTIVE: To determine if two ceftriaxone solutions of different concentrations are bioequivalent when administered intramuscularly. DESIGN: Double-blind, single-dose, two-period, randomized crossover study. SETTING: A clinical research center. SUBJECTS: Seventeen healthy volunteers. INTERVENTION: Ceftriaxone 500 mg administered in either 2 or 1.4 mL of lidocaine 1% solution, with final ceftriaxone concentrations of 250 and 350 mg/mL, respectively. MAIN OUTCOME MEASURES: Blood samples were assayed for ceftriaxone concentrations with HPLC and pharmacokinetic parameters were calculated from the resulting plasma—concentration time profiles: maximum plasma concentration (Cmax) of ceftriaxone and areas under the concentration-time curve (AUC) from 0 to 36 h and 0 to infinity were the primary parameters considered in the determination of bioequivalence. RESULTS: The two solutions were generally well tolerated and had similar safety profiles. Administration of both solutions resulted in similar mean values for all pharmacokinetic parameters. Statistical analysis showed no significant differences between the two solutions in any pharmacokinetic parameter, indicating that the two solutions are statistically bioequivalent (p ≤ 0.05). The 90% CI for the ratio of the means for AUC0-36 (0.86 to 1.11), AUC0-∞. (0.89 to 1.14), and Cmax (0.84 to 1.12) are within the Food and Drug Administration range of bioequivalence (0.80 to 1.25). CONCLUSIONS: These results demonstrate that the more concentrated solution of ceftriaxone (350 mg/mL) is bioequivalent to the currently marketed solution of 250 mg/mL.

An Evaluation of the Potential for Pharmacokinetic Interaction between Tramadol and Cytochrome P450 2D6 Inhibitor Promethazine

2014 ◽  
Vol 989-994 ◽  
pp. 1041-1043
Author(s):  
Ping Liu ◽  
Liang Sun ◽  
Jian Zhang ◽  
Rui Chen Guo
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Pharmacokinetic Interaction ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Open Label ◽  
Tramadol Hydrochloride ◽  
Time Curve

In this single-center, randomized, open-label, 3-way crossover study, subjects received each of the following: a single dose of Tramadol Hydrochloride Injection (THI) 35 mg, a single dose of Promethazine Hydrochloride Injection (PHI) 45 mg, and single dose of Compound Tramadol Hydrochloride Injection (CTHI) 80mg. Blood was collected and plasma was analyzed for the pharmacokinetic parameters (maximum plasma concentration [Cmax], time to Cmax [Tmax], area under the plasma concentration-time curve, plasma elimination half-life, clearance, and apparent volume of distribution) of Tramadol and Promethazine. In general, several pharmacokinetic interactions were observed between Tramadol and Promethazine in the present study.

scholarly journals Pharmacokinetics and tolerability of inhaled levodopa from a new dry-powder inhaler in patients with Parkinson’s disease

2019 ◽  
Vol 10 ◽  
pp. 204062231985761 ◽  
Author(s):  
Marianne Luinstra ◽  
Wijnand Rutgers ◽  
Teus van Laar ◽  
Floris Grasmeijer ◽  
Anja Begeman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Concentration ◽  
Dry Powder Inhaler ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Dry Powder ◽  
Time Curve ◽  
Concentration Time ◽  
Dose Response Study

Background: Inhaled levodopa may quickly resolve off periods in Parkinson’s disease. Our aim was to determine the pharmacokinetics and tolerability of a new levodopa dry-powder inhaler. Methods: A single-centre, single-ascending, single-dose–response study was performed. Over three visits, eight Parkinson’s disease patients (not in the ‘off state’) received by inhalation 30 mg or 60 mg levodopa, or their regular oral levodopa. Maximum levodopa plasma concentration ( Cmax), time to maximum plasma concentration (Tmax) and area under the concentration time curve 0–180 min were determined. Spirometry was performed three times at each visit. Results: After inhalation, levodopa Tmax occurred within 15 min in all participants, whereas after oral administration, Tmax ranged from 20 min to 90 min. The bioavailability of inhaled levodopa without carboxylase inhibitor was 53% relative to oral levodopa with carboxylase inhibitor. No change in lung-function parameters was observed and none of the patients experienced cough or dyspnoea. No correlation was observed between inhalation parameters and levodopa pharmacokinetic parameters. Conclusion: Inhaled levodopa is well tolerated, absorbed faster than oral levodopa, and can be robustly administered over a range of inhalation flow profiles. It therefore appears suitable for the treatment of off periods in Parkinson’s disease.

scholarly journals Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

2017 ◽  
Vol 67 (3) ◽  
pp. 357-371 ◽  
Author(s):  
Fengling Wang ◽  
Jin Chen ◽  
Wenting Dai ◽  
Zhengmin He ◽  
Dandan Zhai ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Lung Adenocarcinoma ◽  
Anticancer Activity ◽  
Targeted Delivery ◽  
A549 Cells ◽  
Nanostructured Lipid Carriers ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Time Curve

AbstractIn order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p> 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activityin vitroagainst A549 cells than native curcumin (IC50value of 5.66vs.9.81 mg L−1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.

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