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.

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 Effect of Concomitant Artesunate Administration and Cytochrome P4502C8 Polymorphisms on the Pharmacokinetics of Amodiaquine in Ghanaian Children with Uncomplicated Malaria

2008 ◽  
Vol 52 (12) ◽  
pp. 4400-4406 ◽  
Author(s):  
George O. Adjei ◽  
Kim Kristensen ◽  
Bamenla Q. Goka ◽  
Lotte C. G. Hoegberg ◽  
Michael Alifrangis ◽  
...  
Keyword(s):  
Body Weight ◽  
Uncomplicated Malaria ◽  
Population Distribution ◽  
Parasite Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Maximum Plasma ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Wide Variability

ABSTRACT Artesunate (AS) is used in combination with amodiaquine (AQ) as first-line treatment for uncomplicated malaria in many countries. We investigated the effect of concomitant AS administration on the pharmacokinetics of AQ and compared concentrations of desethylamodiaquine (DEAQ), the main metabolite of AQ, in plasma between patients with different variants of the cytochrome P4502C8 (CYP2C8) gene. A two-compartment model was fitted to 169 plasma DEAQ concentrations from 103 Ghanaian children aged 1 to 14 years with uncomplicated malaria treated either with AQ alone (n = 15) or with AS plus AQ (n = 88). The population clearance of DEAQ appeared to increase nonlinearly with body weight, and the central volume of distribution of DEAQ was higher (P < 0.001) in the AS-plus-AQ group than in the AQ-only group. The maximum plasma DEAQ concentration was higher (P < 0.001), and the population distribution half-life was shorter (P < 0.01), in the AQ-only group than in the AS-plus-AQ group. The total areas under the plasma DEAQ concentration-time curves (P = 0.68) and elimination half-lives (P = 0.39) were similar for the two groups. There was a high frequency (0.179) of the non-wild-type allele of CYP2C8, but no differences between CYP2C8 genotypes with regard to AQ efficacy or safety were evident. The sample size, however, was limited, so monitoring of AQ toxicity in the study area is still indicated. The nonlinear clearance of DEAQ and the wide variability in kinetic parameters have safety implications for weight-based dosing of higher-body-weight children with AQ. The pharmacokinetics of artemisinin combination therapies should be studied in malaria patients, because the rapid parasite clearance caused by the artemisinin may affect the kinetics of the partner drug and the combination.

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 Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study

2010 ◽  
Vol 65 (11) ◽  
pp. 2445-2449 ◽  
Author(s):  
S. Dominguez ◽  
J. Ghosn ◽  
G. Peytavin ◽  
M. Guiguet ◽  
R. Tubiana ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Liver Fibrosis ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

Preparation and pharmacokinetics of cefquinome sulfate liposomes in goats

2018 ◽  
Author(s):  
Haigang Wu ◽  
Jinni Liu ◽  
Gugangke Xu ◽  
Zhaowei Ye ◽  
Jicheng Liu and Benchi Yi
Keyword(s):  
Plasma Concentration ◽  
Particle Diameter ◽  
Entrapment Efficiency ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Average Particle ◽  
Average Particle Diameter ◽  
Ethanol Injection ◽  
Elimination Half ◽  
Time Point

We evaluated the pharmacokinetics of cefquinome sulfate (CEF) liposomes in eight healthy goats following intramuscular administration at 4 mg/kg. The average particle diameter of CEF liposomes prepared by the ethanol injection method was 335nm with a CEF entrapment efficiency of 69.56%. The elimination half-life (t1/2b) of CEF liposomes was 33.04h compared with 16.21 h for CEF injected without carrier (p less than 0.05). The area under the concentration curve (AUC) for CEF liposomes was approximately three-times greater than for CEF alone (P less than 0.05). The time-point of maximum plasma concentration of the drug (Tp) and the maximum plasma concentration (Cmax) were 4.38 h and 1.99 ìg/mL for CEF liposomes, compared with 1.86 h and 3.55 ìg/mL for CEF without carrier, respectively. 

A Study of the Acid Dose-Response Curve to Small Doses of Pentagastrin in Duodenal Ulcer Patients

1972 ◽  
Vol 43 (2) ◽  
pp. 181-191
Author(s):  
J. B. Elder ◽  
G. Gillespie ◽  
E. H. G. Campbell ◽  
I. E. Gillespie ◽  
G. P. Crean ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Body Weight ◽  
Dose Response ◽  
Response Curve ◽  
Acid Output ◽  
Twilight Zone ◽  
Response Curves ◽  
Small Doses ◽  
Threshold Doses ◽  
Body Weight Dose

1. The acid secretory responses to a range of small doses of pentagastrin in 0·15 m-NaCl have been studied in thirty-one preoperative duodenal ulcer subjects. Acid output increased significantly above basal values when a dose of 0·064 μg h−1 kg−1 was given. 2. Control observations in sixteen duodenal ulcer patients using the saline solvent alone at identical rates of infusion showed no significant increase in acid output. 3. From the dose-response curves sub-threshold and threshold doses of pentapeptide are suggested for duodenal ulcer patients before truncal vagotomy. 4. Considerable variation in acid response was noted between patients given the same body-weight dose of pentapeptide. The results suggest that a ‘twilight zone’ of stimulation exists between the dose of pentagastrin by which few patients are stimulated and the dose by which the majority are stimulated. This may reflect some variation in the sensitivity to stimulation by pentagastrin from one patient to another.

scholarly journals Drug plasma trough concentrations during treatment with daclatasvir and sofosbuvir are associated respectively with liver impairment and with renal dysfunction in HIV/HCV co-infected patients

2019 ◽  
Author(s):  
Ilaria Mastrorosa ◽  
Massimo Tempestilli ◽  
Stefania Notari ◽  
Patrizia Lorenzini ◽  
Gabriele Fabbri ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Virologic Response ◽  
Patient Treatment ◽  
Limited Information ◽  
Plasma Drug ◽  
Related Factors ◽  
Immunological Parameters ◽  
Liver Impairment ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

Abstract Background Sofosbuvir (SOF) plus daclatasvir (DCV) achieved high rates of sustained virologic response (SVR) with no difference according to HIV serostatus. Only limited information is available on the pharmacokinetics variability of SOF and DCV in HIV/HCV co-infected patients. Aim was to evaluate the association of plasma drug concentrations (Ctrough) of SOF and of DCV with patient-, treatment-, and disease-related factors in the real-world setting of HIV/HCV co-infected persons. Methods HIV/HCV co-infected patients, undergoing SOF plus DCV treatment, were prospectively enrolled. At baseline, week4 (W4), end of treatment (EOT), and after-EOT, biochemical and viro-immunological parameters were assessed. FIB-4 score and CKD-EPI equation were used for estimation of liver disease and glomerular filtration rate (eGFR), respectively. SOF, SOF metabolite (GS-331007), and DCV Ctrough were measured at W4 and week8 (W8), and the mean value (mean-Ctrough) was calculated Results Thirty-five patients were included (SVR 94%). Increasing GS-331007 mean-Ctrough significantly correlated with decreasing eGFR at W4 (rho=-0.36; p=0.037) and EOT (rho=-0.34; p=0.048). Between DCV mean-Ctrough and FIB-4, a significant correlation was observed at all time-points: baseline (rho=-0.35; p=0.037), W4 (rho=-0.44; p=0.008), EOT (rho=-0.40; p=0.023), after-EOT (rho=-0.39; p=0.028). Conclusion In HIV/HCV co-infected patients receiving SOF plus DCV, plasma drug concentrations are associated with renal dysfunction for GS-331007 and with liver impairment for DCV. Though clinical and therapeutically relevance of these findings may apparently be limited, growth of clinicians’ knowledge on DAA exposure in difficult-to-treat patients, as cirrhotic and renal impaired subjects, can be relevant in single cases.

scholarly journals Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

2005 ◽  
Vol 49 (6) ◽  
pp. 2421-2428 ◽  
Author(s):  
Douglas N. Fish ◽  
Isaac Teitelbaum ◽  
Edward Abraham
Keyword(s):  
High Performance ◽  
Continuous Venovenous Hemofiltration ◽  
Systemic Clearance ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Infusion ◽  
Dosing Interval ◽  
Adult Intensive Care Unit ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Higher Doses

ABSTRACT The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n = 6 patients) or hemodiafiltration (CVVHDF; n = 6 patients). Patients (mean ± standard deviation age, 50.9 ± 15.9 years; weight, 98.5 ± 15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL S ) and elimination half-life (t 1/2) of imipenem were 145 ± 18 ml/min and 2.7 ± 1.3 h during CVVH versus 178 ± 18 ml/min and 2.6 ± 1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL S , respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 μg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC = 4 to 8 μg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.

scholarly journals Single-Dose Pharmacokinetics of Meropenem during Continuous Venovenous Hemofiltration

1998 ◽  
Vol 42 (9) ◽  
pp. 2417-2420 ◽  
Author(s):  
Florian Thalhammer ◽  
Peter Schenk ◽  
Heinz Burgmann ◽  
Ibrahim El Menyawi ◽  
Ursula M. Hollenstein ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Continuous Venovenous Hemofiltration ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Pharmacokinetic Properties ◽  
Severe Infections ◽  
Total Body ◽  
Trough Levels ◽  
Body Clearance

ABSTRACT The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 ± 18.6 ml/min and 2.46 ± 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 ± 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 ± 2.7 μg/ml, and trough levels after 6 h of CVVH were 6.6 ± 1.5 μg/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 ± 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

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