Evaluation of Pharmacokinetic Interaction of Cilostazol with Metoclopramide after Oral Administration in Human

2019 ◽  
Vol 20 (11) ◽  
pp. 924-928 ◽  
Author(s):  
Iram Kaukab ◽  
Syed Nisar Hussain Shah ◽  
Zelal Kharaba ◽  
Ghulam Murtaza ◽  
Abubaker Ali Saad ◽  
...  
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Plasma Drug Concentration ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Two Phase ◽  
Time Period ◽  
Maximum Plasma Drug Concentration ◽  
The Mean

Background: Metoclopramide is mainly metabolized by CYP2D6, CYP3A4, CYP2C19, and CYP1A2 enzymes, while cilostazol is also metabolized by CYP3A4, CYP2C19, and CYP1A2 enzymes. Aim: This study evaluates the effect of cilostazol on the pharmacokinetics of oral metoclopramide. Methods: This was a randomized, two-phase cross-over pharmacokinetic study separated by a 4-week wash-out time period, 12 healthy non-smoking volunteers received metoclopramide 20 mg as a single oral dose and after 4 weeks, cilostazol 100 mg twice daily for 4 days then with metoclopramide 20 mg on test day. Serial blood samples were analyzed by using a validated high-performance liquid chromatography-ultraviolet method to determine maximum plasma drug concentration (Cmax), time to reach (Tmax), and area under the curve (AUC0-∞) of metoclopramide. Results: Cilostazol increased the mean Cmax, AUC0-∞ and half-life (T1/2) of metoclopramide by 6%, 27% and by 0.79 %, respectively. In addition, Tmax of metoclopramide was delayed by cilostazol. Conclusion: The results showed delayed Tmax of metoclopramide by cilostazol, which could lead to the conclusion that cilostazol affects the absorption of metoclopramide. Both drugs when necessary to administer together must not be administered at the same time especially when given in gastroparesis patients.

scholarly journals Evaluation of the pharmacokinetic interaction and safety of ubrogepant coadministered with acetaminophen or nonsteroidal anti-inflammatory drugs: A randomized trial

2020 ◽  
Vol 3 ◽  
pp. 251581632092118 ◽  
Author(s):  
Abhijeet Jakate ◽  
Ramesh Boinpally ◽  
Matthew Butler ◽  
Kaifeng Lu ◽  
Kristi Womack ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Geometric Mean ◽  
Plasma Drug Concentration ◽  
Migraine Treatment ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Two Phase ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Healthy Participants

Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist approved by the US Food and Drug Administration for acute treatment of migraine with or without aura in adults. Objectives: To assess potential pharmacokinetic (PK) drug–drug interactions in healthy participants and inform the safety and tolerability of ubrogepant alone and in combination with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy participants and participants with migraine. Methods: Two phase 1, three-way crossover studies randomized healthy adults to 100 mg ubrogepant alone, 1000 mg acetaminophen or 500 mg naproxen alone, and 100 mg ubrogepant plus 1000 mg acetaminophen or 500 mg naproxen. Geometric mean ratios (GMRs) and 90% confidence intervals were calculated based on statistical comparison of maximum plasma drug concentration ( C max) and area under the plasma drug concentration–time curve (AUC) for treatment in combination versus alone. Two phase 3 randomized trials included adults with migraine. Treatment-emergent adverse events (TEAEs) were evaluated. Results: Time to C max and terminal elimination half-life for all treatments were unchanged when coadministered. Ubrogepant C max and AUC increased by approximately 40% when coadministered with acetaminophen. Acetaminophen C max decreased by 24% (GMR = 0.76) when coadministered with ubrogepant. There were no significant PK interactions between ubrogepant and naproxen. TEAE rates in the acetaminophen and NSAID rescue medication groups were similar to ubrogepant alone. Conclusions: Coadministration of ubrogepant and acetaminophen resulted in a statistically significant increase in ubrogepant exposure and a decrease in acetaminophen C max; however, these changes were not clinically relevant. No statistically or clinically relevant changes in PK were associated with ubrogepant and naproxen coadministration. No safety concerns were identified for ubrogepant alone or in combination with acetaminophen or NSAIDs.

scholarly journals Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in patients with Lassa fever in Nigeria

BMJ Open ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. e036936
Author(s):  
Cyril Erameh ◽  
Osahogie Edeawe ◽  
Peter Akhideno ◽  
Gloria Eifediyi ◽  
Till F Omansen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Ethics ◽  
Drug Concentration ◽  
Health Research ◽  
Systemic Disease ◽  
Lassa Fever ◽  
Plasma Drug Concentration ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Maximum Plasma Drug Concentration

IntroductionLassa fever (LF) is a severe and often fatal systemic disease in humans and affects a large number of countries in West Africa. Treatment options are limited to supportive care and the broad-spectrum antiviral agent ribavirin. However, evidence for ribavirin efficacy in patients with LF is poor and pharmacokinetic (PK) data are not available.Irrua Specialist Teaching Hospital (ISTH) developed an intravenous ribavirin regimen different to the WHO recommendation. Apart from a lower total daily dose the drug is usually administered once per day which reduces the exposure of personnel to patients with LF. The aim of this study is to characterise the PK of the Irrua ribavirin regimen.Methods and analysisThis prospective, observational clinical study will assess PK properties of the Irrua ribavirin regimen on routinely ribavirin-treated patients with LF at ISTH, a referral hospital serving 19 local governmental areas in a LF endemic zone in Nigeria. Participants will be adults with PCR-confirmed LF. The primary objective is to describe classical PK parameters for ribavirin (maximum plasma drug concentration, time to maximum plasma drug concentration, area under the plasma drug concentration vs time curve, half-life time T1/2, volume of distribution). Blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10 of ribavirin treatment. Ribavirin plasma concentrations will be determined using liquid chromatography coupled to tandem mass spectrometry.Ethics and disseminationThe study will be conducted in compliance with the protocol, the Declaration of Helsinki, Good Clinical Practice (GCP) and the Nigerian National Code for Health Research Ethics. The protocol has received approval by the Health Research Ethics Committee of ISTH. Results will be made available to LF survivors, their caregivers, the funders, LF research society and other researchers.Registration detailsISRCTN11104750

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

Increased teniposide clearance with concomitant anticonvulsant therapy.

1992 ◽  
Vol 10 (2) ◽  
pp. 311-315 ◽  
Author(s):  
D K Baker ◽  
M V Relling ◽  
C H Pui ◽  
M L Christensen ◽  
W E Evans ◽  
...  
Keyword(s):  
High Performance ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Substantial Reduction ◽  
Systemic Exposure ◽  
Pharmacokinetic Interaction ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Systemic Clearance ◽  
The Mean

PURPOSE A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients. PATIENTS AND METHODS The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data. RESULTS The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P less than .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients. CONCLUSION These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.

Pharmacokinetics and suggested oral dosing regimen of cisapride: a study in healthy cats

1997 ◽  
Vol 33 (6) ◽  
pp. 517-523 ◽  
Author(s):  
SN LeGrange ◽  
DM Boothe ◽  
S Herndon ◽  
MD Willard
Keyword(s):  
Body Weight ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Routes Of Administration ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Maximum Plasma Drug Concentration ◽  
Random Crossover ◽  
Body Weight Dose ◽  
Oral Capsule

The disposition of cisapride in seven healthy cats was determined following administration of either a single oral (2 mg/kg body weight) or intravenous (i.v.) (1 mg/kg body weight) dose. Cats were studied using a random crossover design. After administration of the oral capsule, maximum plasma drug concentration (Cmax) +/- standard deviation (SD) was 73.32 +/- 16.59 ng/ml, and bioavailability +/- SD was 29.0 +/- 22.6%. Following i.v. administration, extrapolated peak cisapride concentration (C0) +/- SD was 421.30 +/- 155.37 ng/ml, and clearance +/- SD was 15 +/- 0.67 ml/kg per minute. Elimination half-life (T1/2) was similar for both routes of administration (T1/2(oral) +/- SD was 5.27 +/- 3.16 hr, T1/2(i.v.) +/- SD was 5.19 +/- 3.77 hr). Adverse effects were not observed. Based on these results, a dose of 1 mg/kg body weight per os (PO) every eight hours or 1.5 mg/kg body weight every 12 hours is expected to result in plasma drug concentrations within the therapeutic ranges established for humans.

scholarly journals Pharmacokinetic Study of Modafinil in Relation to Gender and Ethnicity in Healthy Young Chinese Volunteers

2010 ◽  
Vol 13 (3) ◽  
pp. 443 ◽  
Author(s):  
Tao Guo ◽  
Longshan Zhao ◽  
Dong-Ya Xia
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
High Performance ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Significant Difference ◽  
Total Body

Purpose. The pharmacokinetics of modafinil were investigated in relation to gender and ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui ( n = 10/group) following administration of a single 200 mg oral dose. Methods. Blood samples were collected over 48 h for the determination of plasma levels of modafinil and its acid metabolite by High performance liquid chromatography with an ultraviolet detector. Pharmacokinetic parameters were evaluated using noncompartmental methods. Results. Modafinil was well tolerated and safe at a single oral dose of 200 mg. All participants reported adverse events, none of which was serious or unexpected. The maximum plasma concentration (Cmax) and area under the curve for modafinil concentration versus time, which was extrapolated to infinity (AUC0-∞), were higher in women compared to men (p < 0.01). No gender-based difference was noted in the total body weight-normalized modafinil oral clearance. The total body weight-normalized modafinil apparent volume of distribution and the t1/2 was found to exhibit an ethnicity-based significant difference. Conclusion. The results of the current study suggest that there might be pharmacokinetic differences related to gender and ethnicity in the pharmacokinetics of modafinil.

scholarly journals Preclinical Monitoring of Drug Association in Experimental Chemotherapy of Chagas' Disease by a New HPLC-UV Method

2012 ◽  
Vol 56 (6) ◽  
pp. 3344-3348 ◽  
Author(s):  
Rodrigo Moreira da Silva ◽  
Líliam Teixeira Oliveira ◽  
Neila Márcia Silva Barcellos ◽  
Jacqueline de Souza ◽  
Marta de Lana
Keyword(s):  
Chagas Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Volume Of Distribution ◽  
Experimental Chemotherapy ◽  
Content Type ◽  
Therapeutic Regime ◽  
Significant Difference

ABSTRACTA combination of drugs in experimental chemotherapy of Chagas' disease may increase the effectiveness of treatment. To evaluate the possible mechanisms that influence the improvement of therapy, we investigated the pharmacokinetic interaction between benznidazole and itraconazole in a murine model treated orally with single doses of 5 mg of each compound separately or together. Blood samples from treated mice were collected at different intervals for 48 h, and a high-performance liquid chromatography (HPLC)-UV method was used to quantify both drugs in the plasma. A decrease of 1.5-fold in the maximum drug concentration in the plasma (Cmax) and an increase of 2.66-fold in the volume of distribution (V) and 7.5-fold in the elimination half-life (t1/2β) of benznidazole when coadministered with itraconazole were observed. The parameters area under the curve (AUC0-t), area under the curve extrapolated to infinity (AUC0-∞), time to maximum concentration of drug in serum (Tmax), and clearance (CL) for benznidazole were not significantly different in this therapeutic regime. None of the evaluated parameters for ITC demonstrated a significant difference between isolated and associated administration. These results suggest that the main effect of this interaction leads to accumulation of benznidazole in the biological system. This effect may contribute to the improved therapeutic efficacy of this combination of drugs, in addition to synergism of the different mechanisms of action of benznidazole and itraconazole againstTrypanosoma cruzi in vivo.

Lack of Pharmacokinetic Interaction Between the Antimigraine Compound, Almotriptan, and Propranolol in Healthy Volunteers

Cephalalgia ◽  
2001 ◽  
Vol 21 (1) ◽  
pp. 61-65 ◽  
Author(s):  
JC Fleishaker ◽  
TA Sisson ◽  
BJ Carel ◽  
NE Azie
Keyword(s):  
High Performance ◽  
Treatment Effects ◽  
Vital Signs ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Concomitant Administration ◽  
Crossover Design ◽  
Pharmacokinetic Parameters ◽  
Percent Confidence Interval ◽  
Healthy Male

This study was designed to assess the pharmacokinetics of almotriptan, a 5-HT1B/1D agonist, when administered in the presence and absence of propranolol. Healthy male ( n = 10) and female ( n = 2) volunteers received (i) 80 mg propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii) 12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by high performance liquid chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance (anova). Statistically significant differences between treatments in area under the curve (AUC), clearance, and half-life were observed ( P < 0.03), but these differences were < 7%. Ninety percent confidence interval analysis of log-transformed pharmacokinetic parameters showed that the treatments were equivalent. Adverse events were mild to moderate in intensity, and no treatment effects on vital signs were observed. The results show that propranolol has no effect on the pharmacokinetics of almotriptan. Concomitant administration of the two drugs is well tolerated.

scholarly journals Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 931
Author(s):  
Philipp Simon ◽  
David Petroff ◽  
David Busse ◽  
Jana Heyne ◽  
Felix Girrbach ◽  
...  
Keyword(s):  
Half Life ◽  
High Performance ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Controlled Clinical Trial ◽  
Morbidly Obese ◽  
Maximum Plasma ◽  
The Impact

Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m2) and age-/sex-matched nonobese (18.5 kg/m2 ≥ BMI ≤ 30 kg/m2) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 ± 11 kg/m2) and 15 nonobese (BMI 24 ± 2 kg/m2) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: −18.3 to −3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6–9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, −1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05–0.37) and fairly similar area under the curve (AUC)8h (78.7 vs. 89.2 mg*h/L, −21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, −16.8 to −0.8) but not the AUC8h (28.5 vs. 42.0 mg*h/L, −33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25–8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary.

Effects of humerus intraosseous versus intravenous amiodarone administration in a hypovolemic porcine model

2016 ◽  
Vol 11 (4) ◽  
pp. 261-269 ◽  
Author(s):  
Monica M. Holloway, BSN ◽  
Shannan L. Jurina, MSN ◽  
Joshua D. Orszag, BSN ◽  
George R. Bragdon, MS ◽  
Rustin D. Green, BSN, CCRN ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
High Performance ◽  
Spontaneous Circulation ◽  
Maximum Plasma ◽  
Life Saving ◽  
Maximum Plasma Drug Concentration ◽  
Liquid Chromatography Tandem Mass ◽  
Intravenous Amiodarone ◽  
Repeated Analysis ◽  
Over Time

Objective: To compare the effects of amiodarone administration by humerus intraosseous (HIO) and intravenous (IV) routes on return of spontaneous circulation (ROSC), time to maximum concentration (Tmax), maximum plasma drug concentration (Cmax), time to ROSC, and mean concentrations over time in a hypovolemic cardiac arrest model.Design: Prospective, between subjects, randomized experimental design.Setting: TriService Research Facility.Subjects: Yorkshire-cross swine (n = 28).Intervention: Swine were anesthetized and placed into cardiac arrest. After 2 minutes, cardiopulmonary resuscitation was initiated. After an additional 2 minutes, amiodarone 300 mg was administered via the HIO or the IV route. Blood samples were collected over 5 minutes. The samples were analyzed using high-performance liquid chromatography tandem mass spectrometry.Main Outcome Measurements: ROSC, Tmax, Cmax, time to ROSC, and mean concentrations over time.Results: There was no difference in ROSC between the HIO and IV groups; each had five achieve ROSC and two that did not (p = 1). There was no difference in Tmax (p = 0.501) or in Cmax between HIO and IV groups (p = 0.232). Means ± standard deviations in seconds were 94.3 ± 78.3 compared to 115.7 ± 87.3 in the IV versus HIO groups, respectively. The mean ± standard deviation in nanograms per milliliter for the HIO was 49,041 ± 21,107 and 74,258 ± 33,176 for the IV group. There were no significant differences between the HIO and IV groups relative to time to ROSC (p = 0.220). A repeated analysis of variance indicated that there were no significant differences between the groups relative to concentrations over time (p 0.05).Conclusion: The humerus intraosseous provides rapid and reliable access to administer life-saving medications during cardiac arrest.

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