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 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.

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.

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.

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.

Pharmacokinetics, safety and tolerability of ravidasvir, with and without danoprevir/ritonavir, in healthy subjects

2021 ◽  
Author(s):  
Guolan Wu ◽  
Huili Zhou ◽  
Jing Wu ◽  
Duo Lv ◽  
Lihua Wu ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Fold Increase ◽  
Sequential Design ◽  
Maximum Plasma ◽  
Double Blind ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Multiple Doses

Ravidasvir (RDV) is a novel oral hepatitis C virus NS5A inhibitor. This study aimed to evaluate the pharmacokinetics and safety of RDV and the drug–drug interaction between RDV and ritonavir-boosted danoprevir (DNVr) in healthy adults. In 1 st study, healthy volunteers were administered oral single doses of 100, 200 and 300 mg RDV and 200 mg once daily for 7 days. The 2 nd study was randomized, double-blind and placebo-controlled sequential design (day 1 for 200 mg RDV alone, day 7 for 100 mg/100 mg DNVr, day 13 for 200 mg RDV plus 100mg/100mg DNVr, followed by RDV 200 mg once daily with DNVr 100mg/100mg twice daily for 10 days). The results showed that RDV exposure increased in a dose-proportional manner following a single dose with no evidence of accumulation with multiple doses. Co-administration with DNVr regimen (100 mg/100 mg, twice daily) resulted in a 2.92- and 1.99-fold increase in minimum plasma concentration at steady state (C min,ss ) and area under the concentration–time curve at steady state (AUC τ ) of RDV. With co-administration of RDV, maximum plasma concentration (C max ) and area under the concentration curve from zero to 12 h (AUC 0-12 ) of DNV increased 1.71-fold and 2.33-fold, respectively. We did not observe any significant changes in ritonavir exposure. Both single and multiple doses of RDV with or without DNVr were well tolerated. The favorable pharmacokinetic and safety results support ravidasvir’s continued clinical development and treatment.

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 Safety and pharmacokinetic profile of pretomanid (PA-824) in healthy Chinese participants: Results of a phase I single dose escalation study

2021 ◽  
Author(s):  
Yue Liu ◽  
Yan Tan ◽  
Gang Wei ◽  
Zhifei Lu ◽  
Yazhou Liu ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Phase I ◽  
Dose Escalation ◽  
Pharmacokinetic Profile ◽  
Primary Objective ◽  
Maximum Plasma ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Chinese Populations ◽  
Healthy Chinese

Abstract We investigated the safety, tolerability and pharmacokinetic (PK) profile of pretomanid (formerly PA-824) in healthy Chinese volunteers. This was a single-center, double-blind, placebo-controlled, phase I dose escalation study, in which healthy volunteers were consecutively allocated to increasing pretomanid dose groups (50, 100, 200, 400, 600, 800, or 1000 mg) and randomized to receive pretomanid or matching placebo. The primary objective was to evaluate the safety, tolerability and PK profile of pretomanid. In total, 306 volunteers were screened, and 60 were assigned to treatment (pretomanid: n=46, placebo: n=14) of whom 83.3% were male, age ranged from 19-39 years and BMI ranged from 19.2-25.9 kg/m2. At least one adverse event (AE) was reported by 67.4% of patients assigned to pretomanid and 50.0% of those who received placebo, there were no serious AEs or AEs leading to withdrawal. Drug-related events that occurred in ≥5% of participants assigned to pretomanid were proteinuria (26.1%), hematuria (15.2%), conjugated hyperbilirubinemia (6.5%), hyperbilirubinemia (6.5%) and elevated uric acid (6.5%). No relationship between pretomanid dose and AEs was observed. In the PK analysis (n=46), maximum pretomanid plasma concentration was reached in a mean of 4 hours in all dose groups except 800 mg (12 hours) and the plasma half-life ranged from 20.2-25.2 hours. No dose proportionality was observed for maximum plasma concentration, or area under the plasma concentration curve. In conclusion, single pretomanid doses from 50-1000 mg were well tolerated in healthy Chinese participants and the PK profile was generally consistent with findings in non-Chinese populations.

Comparative Study of Bioavailability and Clinical Efficacy of Carbamazepine in Epileptic Patients

1997 ◽  
Vol 31 (5) ◽  
pp. 548-552 ◽  
Author(s):  
Orawan Silpakit ◽  
Montri Amornpichetkoon ◽  
Sming Kaojarern
Keyword(s):  
Plasma Concentration ◽  
Adult Patients ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Psychiatric Facility ◽  
Double Blind ◽  
Three Phase ◽  
Steady State Plasma Concentration ◽  
Blood Specimens ◽  
Patients With Epilepsy

OBJECTIVE: To compare the bioavailability of three generic brands of carbamazepine tablets with that of a proprietary brand in adult patients with epilepsy. DESIGN: A double-blind, randomized, three-phase crossover study. SETTING: A psychiatric facility. PARTICIPANTS: Eighteen patients with epilepsy who had taken carbamazepine at least 5 months before entering the study. MAIN OUTCOME MEASURES: Ten blood specimens from each patient were collected at steady-state. Plasma concentration of carbamazepine was analyzed for pharmacokinetic parameters such as maximum plasma concentration (Cmax), mean time to reach maximum concentration (tmax), and mean AUC. RESULTS: There were no statistically significant differences in these parameters among four brands of carbamazepine. However, when comparing the 90% CI of AUC of three generic brands with that of the proprietary brand, the AUC of two generic brands lay within a range of 80% to 120%. The effects of gender and each brand of carbamazepine on these pharmacokinetic parameters were also analyzed. Breakthrough seizures occurred even though the plasma concentration of carbamazepine was therapeutic. CONCLUSIONS: The bioavailability of two generic brands of carbamazepine tablets (Carmapine and Carzepine) and the proprietary brand (Tegretol) were equivalent in this sample of adult patients with epilepsy.

PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study

2015 ◽  
Vol 262 (6) ◽  
pp. 1515-1525 ◽  
Author(s):  
Marie-Laure Welter ◽  
Adele Demain ◽  
Claire Ewenczyk ◽  
Virginie Czernecki ◽  
Brian Lau ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Double Blind ◽  
Balance Disorders ◽  
Randomised Study

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.

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